Immunobiology最新文献

{"title":"Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia","authors":"Yunyun Du ,&nbsp;Zhenfeng Fan ,&nbsp;Lijiao Li ,&nbsp;Yong Xue ,&nbsp;Shixiang Zhao","doi":"10.1016/j.imbio.2025.153102","DOIUrl":"10.1016/j.imbio.2025.153102","url":null,"abstract":"<div><h3>Background</h3><div>The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.</div></div><div><h3>Methods</h3><div>Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.</div></div><div><h3>Results</h3><div>In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8⁺ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.</div></div><div><h3>Conclusion</h3><div>Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8⁺ T cell expression and increased Treg expression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153102"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656501","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":"Clinical significance of serum miR-98-5p in children with Mycoplasma pneumoniae infection complicated with digestive system damage","authors":"Ying Li ,&nbsp;Wei Jia ,&nbsp;Jiayang Huang ,&nbsp;Jian Liu","doi":"10.1016/j.imbio.2025.153101","DOIUrl":"10.1016/j.imbio.2025.153101","url":null,"abstract":"<div><h3>Background</h3><div>Studies have shown that serum microRNA detection holds significant potential in improving the diagnostic accuracy of <em>mycoplasma pneumoniae</em> pneumonia (MPP).</div></div><div><h3>Aims</h3><div>To investigate the expression and clinical value of miR-98-5p in children with <em>Mycoplasma pneumoniae</em> (MP) infection complicated with diarrhea.</div></div><div><h3>Methods</h3><div>A total of 122 children diagnosed with MPP were selected as study subjects, and 80 healthy children were selected as controls. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of miR-98-5p. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-98-5p. The risk factors for MPP with diarrhea were analyzed by means of a logistic regression model. THP-1 cell models with miR-98-5p overexpression and knockdown were established to investigate the potential mechanisms of miR-98-5p in MP infection.</div></div><div><h3>Results</h3><div>Serum miR-98-5p expression is decreased among children having MPP, and it has a negative correlation with the logMP-DNA level. The miR-98-5p level in children with MPP accompanied by diarrhea is lower compared to that in children with MPP alone. miR-98-5p demonstrates promising diagnostic potential for MPP complicated with diarrhea, and serves as a risk factor for diarrhea in MP-infected children. TargetScan database prediction showed that potential target genes of miR-98-5p, including Synaptotagmin 1 (SYT1) and Tribbles pseudokinase 1(TRIB1), are both associated with digestive system injury induced by MP infection.</div></div><div><h3>Conclusions</h3><div>The expression of serum miR-98-5p is decreased in children with MPP complicated by diarrhea, and it may become a diagnostic biomarker.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153101"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702743","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":"Genetic variants in complement-related genes: potential implications for cancer risk and progression","authors":"Jenny N. Fung ,&nbsp;Ruben Pio","doi":"10.1016/j.imbio.2025.153100","DOIUrl":"10.1016/j.imbio.2025.153100","url":null,"abstract":"<div><div>The complement system is a critical component of the immune system, playing a significant role in pathogen defense and immune regulation. In cancer, it has a complex and dual role, either aiding in immune surveillance or contributing to tumor progression and immune evasion, depending on the specific context. While genetic and epigenetic regulation of complement-related genes has been studied in various diseases, its influence on cancer remains underexplored. This review focuses on how genetic variants in complement pathway genes may modulate cancer susceptibility, progression, and treatment outcomes. Genome-wide association studies (GWAS) have identified several key single nucleotide polymorphisms (SNPs) linked to complement genes, such as <em>C3, C7, CFHR4</em> and <em>ITGB2</em>, which could influence immune responses and cancer development. Additionally, epigenetic modifications, such as DNA methylation, have been shown to regulate the expression of complement genes in cancer, adding further complexity to our understanding of their role in tumor immunity. Challenges remain in translating genetic and epigenetic insights into therapeutic strategies. The complex nature of cancer, tissue-specific complement regulation, and the difficulty in identifying reliable biomarkers complicate the development of targeted complement-based therapies for precision medicine. Therefore, future research combining genetic, genomic, and epigenomic data, along with functional genomics and proteomics, is needed to elucidate the potential roles of regulatory variants of complement genes in cancer. In addition to mechanistic studies, this information can be used to guide personalized treatment strategies for cancer patients.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153100"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662457","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":"B lymphocytes impair osteogenesis by inhibiting BMSC differentiation in osteoporosis","authors":"Cong Peng ,&nbsp;Qiao Yang ,&nbsp;Linyu Li ,&nbsp;Yufeng Li ,&nbsp;Zhaoyang Ye ,&nbsp;Kun Zhao ,&nbsp;Yi Yi ,&nbsp;Liang Wang","doi":"10.1016/j.imbio.2025.153094","DOIUrl":"10.1016/j.imbio.2025.153094","url":null,"abstract":"<div><div><strong>Background:</strong> B lymphocytes have been implicated in the inhibition of osteogenesis, but their role in osteoporosis (OP) remains unclear. This study investigates the association between B lymphocytes and impaired osteogenesis in OP patients and explores the underlying mechanisms. <strong>Methods and materials:</strong> A retrospective analysis of 93 patients with OP assessed the relationship between B lymphocyte counts, bone formation marker Procollagen type I N-terminal propeptide (P1NP), and bone mineral density (BMD). An ovariectomy-induced OP mouse model was established. B lymphocytes and bone marrow mesenchymal stem cells (BMSCs) were isolated and co-cultured to evaluate the impact of B lymphocytes on osteogenic differentiation. Transcriptomic profiling and qPCR were performed to identify key regulatory genes. <strong>Results:</strong> Clinically, B lymphocyte counts were significantly elevated in OP patients with impaired osteogenesis (<em>P</em> &lt; 0.05). Receiver operating characteristic (ROC) analysis indicated diagnostic potential (AUC = 0.638, <em>P</em> &lt; 0.05). In vitro, B lymphocytes reduced Alkaline phosphatase (ALP) activity, calcium deposition, and the expression of osteogenic markers (<em>Osterix, Cbfa1</em>) in BMSCs. Transcriptomic analysis identified 210 differentially expressed genes, among which four (<em>Ccdc170, Extl1, Smpd3, and Thsd4</em>) were validated as potential mediators of B cell-induced osteogenesis inhibition. <strong>Conclusion:</strong> B lymphocytes may impair osteogenesis in OP by suppressing BMSC differentiation. These findings highlight B lymphocytes as potential diagnostic markers and therapeutic targets in osteoporosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153094"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522975","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":"Untargeted metabolomics reveals postoperative metabolic dynamics in hepatic cystic echinococcosis patients","authors":"Kahaer Tuerxun ,&nbsp;Abudouxikuer Abudoumijiti ,&nbsp;Zainuer Yusupu ,&nbsp;Rousitaimujiang Yimamu ,&nbsp;Ronghua Tang ,&nbsp;Ziru Wang ,&nbsp;Abudoukeyimu Yasheng ,&nbsp;Irshat Ibrahim ,&nbsp;Yuanquan Wu","doi":"10.1016/j.imbio.2025.153099","DOIUrl":"10.1016/j.imbio.2025.153099","url":null,"abstract":"<div><h3>Background</h3><div>Hepatic cystic echinococcosis (CE) is a chronic parasitic disease caused by the larval stage of <em>Echinococcus granulosus</em> and remains a significant global zoonosis, particularly in pastoral regions of northwest China. Current diagnostic and postoperative evaluation methods, including imaging, serology, and molecular techniques, lack non-invasive, cost-effective serum biomarkers with high diagnostic accuracy.</div></div><div><h3>Objective</h3><div>This study aimed to investigate dynamic metabolic changes before and after surgery in CE patients using untargeted metabolomics analysis.</div></div><div><h3>Methods</h3><div>Serum metabolites from CE patients were analyzed using ultra-high performance liquid chromatography (UHPLC) and quadrupole time-of-flight high-resolution mass spectrometry. Samples were collected preoperatively and at 1, 4, and 12 weeks postoperatively, alongside samples from healthy controls. Four comparisons were made: preoperative patients vs. healthy controls, and postoperative samples at 1, 4, and 12 weeks vs. preoperative samples. Differential metabolites were identified using bioinformatics analysis, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The key metabolic pathways associated with postoperative recovery were determined by identifying shared enriched pathways across all comparisons. Metabolites in these pathways were further validated using ELISA.</div></div><div><h3>Results</h3><div>The highest number of differential metabolites was observed between preoperative CE patients and healthy controls. Postoperatively, metabolic differences increased with time. KEGG pathway enrichment revealed significant alterations in linoleic acid and arachidonic acid metabolism, both of which are linked to inflammation. ELISA confirmed elevated preoperative levels of leukotrienes, prostaglandins, thromboxanes, and inflammatory cytokines IL-5 and IL-23, which significantly declined after surgery in a time-dependent manner.</div></div><div><h3>Conclusions</h3><div>Untargeted metabolomics identified metabolites closely associated with the arachidonic acid pathway as potential biomarkers for CE diagnosis and postoperative recovery monitoring. These findings provide a foundation for developing non-invasive diagnostic and prognostic tools for hepatic cystic echinococcosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153099"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687075","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":"LINC00461 promotes macrophage M1 polarization by inhibiting KLF4 transcription","authors":"Bicong Gao ,&nbsp;Kaitong Jia ,&nbsp;You Ya ,&nbsp;Rui Tian ,&nbsp;Xiaochen Wang ,&nbsp;Zheng Huang ,&nbsp;Feng Gao","doi":"10.1016/j.imbio.2025.153104","DOIUrl":"10.1016/j.imbio.2025.153104","url":null,"abstract":"<div><h3>Background</h3><div>Macrophage polarization is a complex process whereby macrophages differentiate into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes, mediating distinct and often opposing functions in immunity and tissue repair.</div></div><div><h3>Methods</h3><div>We analyzed LINC00461 expression in M1- and M2-polarized macrophages using qPCR. Functional assays (<em>in vitro</em> and <em>in vivo</em>) were performed to assess the effects of LINC00461 knockdown on cytokine secretion. RNA-seq, bisulfite sequencing, and chromatin immunoprecipitation (ChIP) were used to explore the mechanism involving Kruppel-like factor 4 (KLF4) and DNA methylation.</div></div><div><h3>Results</h3><div>LINC00461 levels were elevated in M1 macrophages and reduced in M2 macrophages. Knockdown of LINC00461 attenuated pro-inflammatory cytokine release (e.g., IL-1β, TNF-α) in M1 cells and promoted anti-inflammatory cytokine secretion (e.g., IL-10, TGF-β) in M2 cells. Mechanistically, LINC00461 knockdown upregulated <em>KLF4</em> transcription, a key M2 polarization regulator. LINC00461 recruited DNA methyltransferases to induce hypermethylation of the <em>KLF4</em> promoter, suppressing KLF4 expression and driving M1 polarization.</div></div><div><h3>Conclusion</h3><div>Our findings establish a functional link between LINC00461, <em>KLF4</em> methylation, and macrophage polarization, providing insights into the epigenetic regulation of inflammatory responses.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153104"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694563","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":"Serum LINC01278 serves as a negative biomarker for sepsis and its up-regulation inhibits LPS-induced inflammatory response in THP-1 cells","authors":"Ying Gu,&nbsp;Honggang Jia,&nbsp;Xinyu Lin,&nbsp;Ling Wang","doi":"10.1016/j.imbio.2025.153098","DOIUrl":"10.1016/j.imbio.2025.153098","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis represents a potentially fatal condition characterized by organ failure. Long non-coding RNAs (lncRNAs) have provided new insights into the treatment of inflammation caused by sepsis.</div></div><div><h3>Aims</h3><div>Exploring the involvement of <em>LINC01278</em> in sepsis and lipopolysaccharide (LPS)-induced inflammatory responses.</div></div><div><h3>Methods</h3><div>A sepsis cell model was established by stimulating THP-1 cells with LPS. Cell proliferation was assessed with the CCK-8 assay, while apoptotic cells were quantified through flow cytometric analysis. The expression of <em>LINC01278</em> and miR-451a, along with the interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), were measured using RT-qPCR and ELISA, respectively. Bioinformatics tools were used to predict the targeting relationship between <em>LINC01278</em> and miR-451a, and their direct interaction was validated by Dual-luciferase reporter assays and RNA immunoprecipitation (RIP).</div></div><div><h3>Results</h3><div>Serum <em>LINC01278</em> expression was significantly lower in 108 sepsis patients than in 105 healthy controls. ROC curve and Kaplan-Meier results indicated that <em>LINC01278</em> had a good diagnostic efficacy for sepsis and was negatively associated with poor prognosis. <em>LINC01278</em> overexpression promoted cell viability, inhibited apoptosis, and reduced the production of IL-6, TNF-α, and IL-1β. Bioinformatics analysis identified miR-451a, which was upregulated in septic patients, as a potential target of <em>LINC01278</em>. Dual-luciferase reporter assays, along with RIP experiments, have verified that <em>LINC01278</em> functions as a competitive endogenous RNA (ceRNA) for miR-451a.</div></div><div><h3>Conclusions</h3><div><em>LINC01278</em> serves as a clinical indicator for both diagnosing sepsis and assessing disease severity. <em>LINC01278</em> exerts protective effects in sepsis by acting as a ceRNA for miR-451a.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153098"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702673","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":"Liyan Kaiyin Formula relieves reflux pharyngitis by regulating M1 macrophage polarization via the NF-κB/NLRP3 pathway","authors":"Lirong Wang ,&nbsp;Xuqing Chen ,&nbsp;Tianyu Xu ,&nbsp;Youpeng Fei ,&nbsp;Qi Yang ,&nbsp;Jingjuan An ,&nbsp;Zeqing Li ,&nbsp;Kunmin Wu","doi":"10.1016/j.imbio.2025.153095","DOIUrl":"10.1016/j.imbio.2025.153095","url":null,"abstract":"<div><div><em>Background:</em> We aimed to investigate whether Liyan Kaiyin Formula (LYKYF) can relieve reflux pharyngitis in rats by regulating M1 macrophage polarization <em>via</em> the nuclear factor-κB (NF-κB)/Nod-like receptor protein 3 (NLRP3) pathway.</div><div><em>Methods:</em> Forty rats were randomized into a sham group, a laryngopharyngeal reflux disease (LPRD) group, a LYKYF group and a LYKYF+CHPG group (<em>n</em> = 10). Enzyme-linked immunosorbent assay was conducted to measure the serum levels of inflammatory factors interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α). Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) were performed to measure the expressions of proteins implicated in NF-κB/NLRP3 pathway. Western blotting was also used for the detection of M1 macrophage markers (CD86 and iNOS).</div><div><em>Results:</em> Compared to the sham group, TNF-α, IL-6 and IL-1β levels in the serum, proportion of M1 macrophages in pharyngeal tissues, p-NF-κB p65/p65 ratio, protein expressions of NLRP3, Caspase-1, Apoptosis-associated speck-like protein (ASC), cluster of differentiation 86 (CD86) and inducible nitric oxide synthase, and mRNA expressions of NF-κB p65, NLRP3, Caspase-1 and ASC in the LPRD group exhibited significant elevations (<em>P</em> &lt; 0.05). Compared with the LYKYF group, the LYKYF+CHPG group had significant elevations in serum TNF-α, IL-6 and IL-1β levels, proportion of M1 macrophages in pharyngeal tissues, p-NF-κB p65/p65 ratio, protein expressions of NLRP3, Caspase-1, ASC, CD86 and iNOS, as well as NF-κB p65, NLRP3, Caspase-1 and ASC mRNA expressions (<em>P</em> &lt; 0.05). The identified key target genes were significantly enriched in GO terms associated with signal transduction, protein phosphorylation regulation, and adaptive responses to external stimuli.</div><div><em>Conclusion:</em> LYKYF may suppress M1 macrophage polarization through suppressing the NF-κB/NLRP3 pathway activation, thereby alleviating reflux pharyngitis in rats.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153095"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518308","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":"Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis","authors":"Bin Wang ,&nbsp;Wenwei Li ,&nbsp;Chaoyang Hong ,&nbsp;Fangfang Jin ,&nbsp;Baisheng Xu ,&nbsp;Zhongwei Guo ,&nbsp;Shuyang Chen ,&nbsp;Qi Zhang","doi":"10.1016/j.imbio.2025.153097","DOIUrl":"10.1016/j.imbio.2025.153097","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is often accompanied by retinal lesions, in which Amyloid β (Aβ) is a key mediator. Vascular dysfunction is always associated with the malignant progression of AD, but the precise mechanisms remain poorly understood. The aim of this study is to investigate how Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis. The research results showed that in the retina of AD model mice, the expression of Aβ and miR-126-5p increased, while the expression of LncRNA-XIST and VEGF decreased. In vitro experiments demonstrated that Aβ treatment downregulated LncRNA-XIST and VEGF expression in RF/6 A cells, while upregulating miR-126-5p and significantly suppressing angiogenesis. Overexpression of LncRNA-XIST can reverse the inhibitory effect of Aβ on angiogenesis, while further overexpression of miR-126-5p can counteract the pro-angiogenic effect of LncRNA-XIST. The dual-luciferase reporter assay results showed that Aβ repressed the transcriptional activity of the LncRNA-XIST promoter by targeting the −800 to −600 fragment. Mechanism studies have revealed that LncRNA-XIST competitively binds to miR-126-5p, preventing its binding to VEGF mRNA and upregulating VEGF expression. In vivo experiments demonstrated that miR-126-5p inhibitor resulted in elevated expression of LncRNA-XIST and VEGF in the mouse retina. This study reveals the molecular mechanism by which Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis, providing a potential new strategy for targeted therapy of AD-related retinal lesions.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153097"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656500","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":"Exosomes derived from baicalin-pretreated bone marrow mesenchymal stem cells inactivate the TLR4/MyD88/NF-kB pathway to improve asthma","authors":"Wenbo Shen ,&nbsp;Wei Jia ,&nbsp;Qiang Wu ,&nbsp;Li Shen ,&nbsp;Yisheng Wang","doi":"10.1016/j.imbio.2025.153103","DOIUrl":"10.1016/j.imbio.2025.153103","url":null,"abstract":"<div><h3>Background</h3><div>Baicalin, a natural compound isolated from the root of <em>Scutellaria baicalensis Georgi</em>, has been shown to have various pharmacological effects on lung diseases including asthma. Recently, research has suggested that baicalin combined with exosomes may have significant potential against disease development. The present work analyzes the effects of exosomes derived from baicalin-pretreated bone marrow mesenchymal stem cells (BMSCs) on asthma and the underlying mechanism.</div></div><div><h3>Methods</h3><div>BALB/c mice were sensitized with ovalbumin (OVA) through intraperitoneal injection to establish an animal model of asthma. Human bronchial epithelial cells (16HBE) were exposed to lipopolysaccharide to mimic a cell model of asthma. The pathological conditions of lung tissues in OVA-induced mice were analyzed by haematoxylin and eosin staining assays. Masson staining and quantification analysis were conducted to analyze percentage of collagen fibers in lung tissues of OVA-induced mice. The Wright-Giemsa assay was used to determine the number of eosinophils, neutrophils, lymphocytes and macrophages. Enzyme-linked immunosorbent assays were performed to analyze expression levels of inflammatory factors including IL-4, IL-5, IL-13 and TNF-α levels. The values of airway resistance (Rrs), elastance (Ers) and compliance (Crs) were recorded for analyzing airway hyperresponsiveness through the FlexiVent system. Protein expression was analyzed by immunohistochemistry (IHC) and/or western blotting assay.</div></div><div><h3>Results</h3><div>Ovalbumin (OVA) pretreatment increased airway inflammation, airway hyperresponsiveness, collagen deposition and epithelial-mesenchymal transition (EMT) in mice, however, these phenomena were significantly improved after treatment with baicalin-pretreated BMSC exosomes. Lipopolysaccharide (LPS)-induced 16HBE cells showed increased levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13) and tumor necrosis factor-α (TNF-α), elevated N-cadherin and Vimentin protein expression, and decreased E-cadherin protein expression, whereas these LPS-induced effects were relieved after treatment with baicalin-pretreated BMSC exosomes. Additionally, protein expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and phosphor p65 (p-p65) was upregulated in lung tissues of OVA-induced mice and LPS-stimulated 16HBE cells, but these phenomena were counteracted following exosomes treatment from baicalin-pretreated BMSCs.</div></div><div><h3>Conclusion</h3><div>Exosomes derived from baicalin-pretreated BMSCs ameliorated airway inflammation, airway hyperresponsiveness and airway remodeling after asthma by inactivating the TLR4/MyD88/nuclear factor kappa B pathway, providing a therapeutic strategy for asthma.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153103"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670606","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}