Mediators of Inflammation最新文献

{"title":"Decoding Fibroblast Heterogeneity in Osteoarthritis: Identification of a Fibrosis-Associated Subtype and Novel Diagnostic Biomarkers.","authors":"Qingpeng Sun, Feng Niu, Li Wang, Honglin Pi, Chongtao Han, Jun Gao","doi":"10.1155/mi/7066432","DOIUrl":"10.1155/mi/7066432","url":null,"abstract":"<p><p><b>Background:</b> Fibroblasts are key contributors to extracellular matrix remodeling and fibrosis, thereby playing a crucial role in the pathogenesis of osteoarthritis (OA). However, their heterogeneity and functional subtypes in OA remain poorly understood. <b>Methods:</b> The single-cell RNA sequencing (scRNA-seq) data of OA and two independent datasets were downloaded from the Gene Expression Omnibus (GEO) database. Subsequently, the Seurat package was utilized to normalize and downscale the scRNA-seq data and classify different cell types. Gene set enrichment analysis (GSEA) was applied to identify significantly enriched biological processes (BPs) specific in each cell cluster. Employing the Monocle2 package, the progression trajectories of OA were analyzed based on the dynamic gene expression changes in the fibroblast subtypes. Finally, single sample GSEA (ssGSEA) and differential expression analysis were combined to screen diagnostic biomarkers for OA, and their diagnostic efficacy was assessed by receiver operating characteristic (ROC) curves and principal component analysis (PCA). <b>Results:</b> Using the scRNA-seq data of OA samples, we identified five different cell types (fibroblasts, endothelial cells [ECs], lymphoid cells, mural cells, and myeloid cells), with fibroblasts accounting for the highest proportion. Then, we found that Fibroblast subtype 3 was notably enriched in fibrosis-related pathways. The pseudotime trajectory analysis showed that genes associated with extracellular matrix and cell adhesion were significantly upregulated during the transformation from healthy status to OA. Additionally, the enrichment score of Fibroblast 3 in the OA tissue was higher than that in healthy tissue, which indicated that fibroblast 3 may promote the development of OA. Finally, four genes (<i>MTUS2</i>, <i>GPR1</i>, <i>GABRA4</i>, and <i>SGCA</i>) with strong diagnostic performance were identified as the biomarkers for OA. <b>Conclusion:</b> The fibroblast subtypes identified by the present research played a critical role in the pathogenesis of OA, and the four biomarkers may serve as new targets for the early diagnosis and treatment of OA.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7066432"},"PeriodicalIF":4.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Kynureninase Attenuates Radiation-Induced Intestinal Injury via MAPK Signaling Suppression.","authors":"Qingxie Liu, Zhi Ling, Yue Zhu, Weijuan Gong, Guotao Lu, Wei Li, Weixuan Yang, Weiming Xiao, Yaodong Wang","doi":"10.1155/mi/7023259","DOIUrl":"10.1155/mi/7023259","url":null,"abstract":"<p><p>Kynureninase (KYNU), a key enzyme in the tryptophan-kynurenine metabolic pathway, has been increasingly recognized for its role in immune regulation and inflammation. However, its involvement in radiation-induced intestinal injury (RIII) has not been fully elucidated. In this study, we identified a significant upregulation of KYNU expression in the colonic tissues of mice with RIII using transcriptomic analysis and experimental validation. Functional assays demonstrated that KYNU knockdown in NCM460 human intestinal epithelial cells attenuated radiation-induced apoptosis and oxidative stress, while promoting cell proliferation. Mechanistically, RNA sequencing (RNA-seq) and pathway enrichment analyses revealed that KYNU regulates the mitogen-activated protein kinase (MAPK) signaling pathway, as KYNU silencing reduced the phosphorylation levels of key MAPK proteins (extracellular signal-regulated kinase [ERK], c-Jun N-terminal kinase [JNK], and p38) following irradiation. Importantly, pharmacological inhibition of KYNU using carbidopa (CBP) significantly mitigated radiation-induced epithelial injury in vitro. In the RIII mouse model, CBP administration (prevention and treatment) increased the number of crypts, improved intestinal epithelial structure, and maintained the integrity of the intestinal barrier. These findings demonstrate, that KYNU plays a critical role in the pathogenesis of RIII and that its inhibition confers protection against intestinal damage by suppressing MAPK-mediated inflammatory responses. Targeting KYNU may thus offer a promising therapeutic strategy for the prevention and treatment of RIII.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7023259"},"PeriodicalIF":4.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Long Noncoding RNA, LOC645166, in T Cells of Ankylosing Spondylitis (AS) Patients Regulates the FOXP3 Expression via the Axis of LOC645166/miR-188-5p/NFKBID.","authors":"Hui-Chun Yu, Kuang-Yung Huang, Ming-Chi Lu, Hsien-Yu Huang Tseng, Ning-Sheng Lai, Hsien-Bin Huang","doi":"10.1155/mi/8574340","DOIUrl":"10.1155/mi/8574340","url":null,"abstract":"<p><p>The expression of long noncoding RNA (LncRNA), LOC645166, is downregulated in T cells of ankylosing spondylitis (AS) patients. The role of LOC645166 in contribution to AS pathogenesis was investigated. Here, we have identified that an interacting network of LOC645166/miR-188-5p/NF-κB inhibitor-D (NFKBID) occurs in T cells of AS patients and regulates the expression of forkhead box P3 (FOXP3). Downregulation of LOC645166 augments the levels of miR-188-5p that binds to the 3'-UTR of NFKB1D mRNA and blocks the NFKB1D expression. NFKB1D, also called IκB_NS, can trigger regulatory T (Treg) cell development through induction of FOXP3 expression. Downregulation of NFKB1D expression leads to suppression of the FOXP3 induction, in turn affecting Treg cell development. Promotion of the autoimmune response induced by suppression of FOXP3 expression contributes to the pathogenesis of AS.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8574340"},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis\".","authors":"","doi":"10.1155/mi/9842314","DOIUrl":"https://doi.org/10.1155/mi/9842314","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2018/5871431.].</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9842314"},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights Into Celastrol's Anti-Pyroptosis Effects in Osteoarthritis via SIRT2 Upregulation.","authors":"Xiaotian Chen, Yining Song, Fan Zhang, Fangyan Hu, Zhenfei Ding, Jianzhong Guan","doi":"10.1155/mi/5676471","DOIUrl":"10.1155/mi/5676471","url":null,"abstract":"<p><p><b>Background:</b> Chronic inflammation and cell apoptosis are hallmark characteristics of osteoarthritis (OA), necessitating the development of novel therapeutic strategies. Celastrol (CSL) has emerged as a promising agent for OA treatment due to its anti-inflammatory properties, but the specific mechanism of action remains unclear. <b>Methods:</b> This study utilized network pharmacology and in vivo experiments to elucidate how CSL modulates the SIRT2-NLRP3 axis in OA. Chondrocytes were treated with CSL to evaluate changes in SIRT2 expression and NLRP3 acetylation levels. OA rats were administered CSL to assess its therapeutic effects. <b>Results:</b> Using network pharmacology and bioinformatics, SIRT2 and NLRP3 were identified as the primary therapeutic targets of CSL for OA. In vitro experiments demonstrated that CSL significantly reduced the levels of inflammatory markers and pyroptosis-related proteins, such as GSDMD-N, in TC28a cells and primary rat chondrocytes (RCs) induced by lipopolysaccharide (LPS) and nigericin (Nig). CSL upregulated SIRT2 expression, decreased NLRP3 acetylation, and promoted anti-inflammatory cytokine expression (IL-4 and IL-10), thereby, reducing inflammation and pyroptosis in chondrocytes. Notably, SIRT2 knockdown reversed CSL's anti-inflammatory and anti-pyroptosis effects. In vivo, CSL significantly alleviated OA symptoms in rats by modulating the SIRT2/NLRP3 pathway. <b>Conclusion:</b> CSL exerts its anti-inflammatory effects in OA by targeting the SIRT2-NLRP3 axis to inhibit chondrocyte pyroptosis. These findings underscore the potential of CSL as a therapeutic agent for mitigating OA progression and offer new insights into its molecular mode of action.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5676471"},"PeriodicalIF":4.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Myeloid Dendritic Cells by Up-Regulating RAGE/JAK/STAT Pathway Induced by Cigarette Smoke Exposure in Mice With Emphysema.","authors":"Jinglin Gao, Huijuan Wang, Guang Zhou, Zhou Zhou, Caixia Liang, Xiaoning Zhong","doi":"10.1155/mi/5595989","DOIUrl":"10.1155/mi/5595989","url":null,"abstract":"<p><p><b>Objective:</b> To explore the potential role of the RAGE/JAK/STAT pathway along with the activation of myeloid dendritic cells (mDCs) and B cells induced by cigarette smoke exposure in mice. <b>Methods:</b> 57BL/6J mice and RAGEfl/flCD11c-Cre mice were subjected to cigarette smoke for 24 weeks and mated with room air controls. Mice bone marrow-derived dendritic cells (BMDCs) were treated with cigarette smoke extracts (CSEs), CSE with the RAGE inhibitor FPS-ZM1 or CSE with the JAK2 inhibitor AG490. The extent of emphysema in these mice was assessed using the average alveolar lining distance (Lm). Real-time PCR was employed to quantify the mRNA expression levels of RAGE, JAK2, STAT1, STAT3 and STAT5 in lung tissue samples. The levels of IL-6 and IL-1β in mouse serum and BMDC supernatant were quantified using ELISA. Flow cytometry was employed to measure the expression of CD40, CD86, RAGE, p-JAK2, p-STAT1, p-STAT3 and p-STAT5 of lung mDCs and BMDCs in mice. Flow cytometry was employed to identify markers CD69, CD86 and CD138 on pulmonary B cells. <b>Results:</b> Exposing mice to cigarette smoke triggered an exaggerated pulmonary mDCs response and elevated the RAGE/JAK/STAT pathway in both pulmonary mDCs and lung tissue, correlating with enhanced B cells response in lungs. Conditional knockdown of RAGE on dendritic cells (DCs) resulted in a reduction of activity within JAK/STAT pathway, impeded the exaggerated mDCs and B cells responses induced by smoking, down-regulated the serum inflammatory response and mitigated emphysema in cigarette smoke-exposed mice. Within a regulated laboratory setting, BMDCs were activated, leading to the amplification of the RAGE/JAK/STAT pathway in these cells after CSE exposure. FPS-ZM1 and AG490 reduced inflammatory factors in the supernatant and activation of BMDC. <b>Conclusion:</b> In mice, prolonged exposure to cigarette smoke triggers the activation of mDCs by enhancing the RAGE/JAK/STAT pathway. Conditional knockdown of RAGE on DCs can prevent the activation of mDCs and B cells triggered by cigarette smoke, indicating that RAGE could be a potential target for treating smoking-induced emphysema.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5595989"},"PeriodicalIF":4.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Medicated Thread Moxibustion of Zhuang Medicine on Skin Lesions in Eczema Rats Based on p38/NF-κB and JAK1-STAT6 Pathways.","authors":"Liangbing Wu, Jian Dai, Yongzheng Wei, Quanrui Jiang, Renkun Huang, Yahui Wang, Xingling Chen, Jiandie Chen, Jinhua Yao, Zhenjie Qiu, Panyu Jiang, Yanyang Zhao, Bingyi Zheng, Wei Lu","doi":"10.1155/mi/9978298","DOIUrl":"10.1155/mi/9978298","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; Eczema is a common inflammatory skin disease that severely affects patients' daily life and work, necessitating effective intervention. Medicated thread moxibustion of Zhuang medicine (MTMZM), an integral part of Chinese medicine, is also a component of complementary and alternative medicine, demonstrating promising therapeutic effects. However, its mechanism in treating eczema remains unknown. Therefore, this study investigated the efficacy and mechanism of MTMZM on skin lesions and p38/NF-κB and JAK1-STAT6 pathway in eczema rats. &lt;b&gt;Methods:&lt;/b&gt; Forty-eight male Sprague-Dawley (SD) rats were randomly divided. Nine of them were assigned to the normal group, while the remaining 39 rats were selected for the subsequent eczema model establishment process. In total, 7% DNCB acetone olive oil solution was used to establish eczema model. Successful modeling rats were randomly divided into three groups with 13 rats each: model group, western medicine group (WM group), and MTMZM group. Normal group and model group received no treatment. MTMZM group received MTMZM treatment on the Ashi point (skin lesions in eczema) and WM group received positive drug Pevisone cream. The eczema severity index (ESI) in rats was scored before intervention and during the first and second weeks of intervention. After intervention, samples were taken from rats' back lesions (taking normal skin in the same area from normal group). After sampling, the skin thickness difference (STD) with normal skin and diseased skin lesions was measured. HE staining was used to observe the tissue morphology of skin lesions. Western blot was used to detect JAK1, p-JAK1, STAT6, p-STAT6, NF-κB p65, p-NF-κB p65, and p-p38 protein content in skin lesions; the serum content of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. &lt;b&gt;Results:&lt;/b&gt; (1) Compared with normal group, model group showed dermal necrosis and inflammatory cell infiltration under light microscopy. The ESI and STD increased (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). JAK1, p-JAK1, STAT6, p-STAT6, NF-κB p65, p-NF-κB p65, and p-p38 protein content in skin lesion increased(&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). The serum content IL-1β, TNF-α, and IL-4 increased (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). (2) Compared with model group, MTMZM group and WM group showed significant improvement in pathological changes. The ESI and STD decreased (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). NF-κB p65, p-NF-κB p65, p-p38, JAK1, p-JAK1, STAT6, and p-STAT6 content (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05) decreased. The serum content IL-1β, TNF-α, and IL-4 decreased (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). (3) Compared with WM group, MTMZM group showed visible neovascularization under light microscopy. The ESI and STD decreased (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). There was no significant difference in p-p38, p-NF-κB p65, JAK1, p-JAK1, STAT6, and p-STAT6 content (&lt;i&gt;p&lt;/i&gt;  &gt; 0.05), as well as in IL-4 content (&lt;i&gt;p&lt;/i&gt;  &gt; 0.05). The serum content IL-1β and TNF-α increased (&lt;i&gt;p&lt;/i&gt;  &lt; 0.05). &lt;b&gt;Conclusion:&lt;/b&gt; MTMZM can effectively reliev","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9978298"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Diagnostic Biomarkers for Myocardial Infarction Using Bioinformatics and Disulfidptosis-Targeted Computational Drug Discovery.","authors":"Haoran Zhang, Ziguang Song, Weitao Shen, Donghui Zhang","doi":"10.1155/mi/5054377","DOIUrl":"10.1155/mi/5054377","url":null,"abstract":"<p><p>Disulfidptosis, a newly discovered form of regulated cell death, is involved in multiple disease processes. This study applied computational methods to identify disulfidptosis-related genes in myocardial infarction (MI). Differentially expressed genes (DEGs) from GSE66360 dataset were screened using the limma package and intersected with genes in weighted gene coexpression network analysis (WGCNA) modules to obtain candidate genes. Biomarkers were selected via support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO), and validated by quantitative real-time (qRT)-PCR, CCK-8, and flow cytometry. Enrichment and immune infiltration analyses were performed using clusterProfiler and CIBERSORT tools. Potential drugs were predicted via the Coremine database and visualized with Cytoscape. Seurat and CellChat packages were employed to perform single-cell transcriptomic analysis and develop cell-cell communication network, respectively. The genes in the lightgreen module that had the highest correlation with immune scores were selected. Next, we identified 10 biomarkers (<i>THBD</i>, <i>IRAK3</i>, <i>NFIL3</i>, <i>IL1R2</i>, <i>THBS1</i>, <i>MAP3K8</i>, <i>JDP2</i>, <i>FCGR2A</i>, <i>CCL20</i>, and <i>EREG</i>), all of which showed significantly higher mRNA levels in AC16-oxygen-glucose deprivation (OGD) cells compared to controls. Silencing <i>MAP3K8</i> and <i>NFIL3</i> enhanced cell viability and reduced apoptosis in AC16-OGD cells. Immune infiltration analysis suggested that <i>NFIL3</i> and <i>MAP3K8</i> modulated T cell function, contributing to MI pathogenesis. Drug analysis predicted 15 candidate drugs targeting both <i>NFIL3</i> and <i>MAP3K8</i>. Single-cell analysis showed that distinguished six cell types in MI, with adipocytes serving as a communication hub interacting closely with cardiomyocytes, fibroblasts, endothelial cells, and macrophages. These findings highlighted the potential of the identified biomarkers as novel therapeutic targets for MI.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5054377"},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Endoplasmic Reticulum Stress-Related Genes in Osteoporosis Pathogenesis.","authors":"Yiren Zhu, Xiu Yang, Yunan Lu, Jiayu He, Bo Liu, Yongfa Zhang, Zhengchao Zhang","doi":"10.1155/mi/6726771","DOIUrl":"10.1155/mi/6726771","url":null,"abstract":"<p><p><b>Background:</b> Osteoporosis is a prevalent metabolic bone disorder with complex molecular underpinnings. Emerging evidence implicates endoplasmic reticulum stress (ERS) in its pathogenesis; however, systematic exploration of ERS-related genes (ERSRGs) remains limited. This study aimed to identify ERS-related differentially expressed genes (ERSRDEGs) in osteoporosis, construct a diagnostic model, and elucidate associated molecular mechanisms. <b>Methods:</b> Three osteoporosis datasets (GSE56815, GSE230665, and GSE7429) were integrated after batch effect correction and normalization. ERSRGs were curated from GeneCards, and ERSRDEGs were identified by intersecting co-differentially expressed genes (Co-DEGs) across datasets. Functional enrichment (gene set enrichment analysis [GSEA], gene set variation analysis [GSVA], Gene Ontology [GO], and Kyoto Encyclopedia of Genes and Genomes [KEGG]) and immune infiltration analyses were performed. Diagnostic models were developed using support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) regression, validated via receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis. Experimental validation included immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in ovariectomized (OVX) mice. Regulatory networks (TF-miRNA-RBP-drug) and protein structure predictions were generated using bioinformatic tools. <b>Results:</b> Fifty six ERSRDEGs were identified, enriched in apoptosis, autophagy, and cytokine signaling pathways. A diagnostic model comprising seven genes (CYB5R4, RAB1B, UFSP2, RNF13, SERP1, CES2, and C1QBP) demonstrated high accuracy (area under the curve (AUC) > 0.9) in both training and validation datasets. Immune infiltration analysis revealed distinct patterns of activated B cells, CD8⁺ T cells, and macrophages between high- and low-risk groups. Regulatory networks highlighted interactions with 52 transcription factors (TFs), 42 miRNAs, and 27 therapeutic compounds. Experimental validation in OVX mice confirmed upregulated expression of C1QBP, CYB5R4, RAB1B, and UFSP2 at protein/mRNA levels, aligning with bioinformatic predictions. <b>Conclusions:</b> This study establishes ERSRDEGs as critical players in osteoporosis pathogenesis and provides a clinically translatable seven-gene diagnostic model for early osteoporosis detection. The integration of multiomics analyses uncovered key pathways, immune dynamics, and regulatory networks, while experimental validation reinforced the role of specific ERSRGs. These findings provide novel insights into ERS-mediated mechanisms and therapeutic targets for osteoporosis management.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6726771"},"PeriodicalIF":4.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture Attenuates Hepatic Ischemia-Reperfusion Injury by Modulating the Esr1/TAK1-JNK/p38 Signaling Pathway in Rats.","authors":"Xiaofang Fan, Wei Guo, Xiaodan Yang, Hao Zhang, Bruno Fink, Lingyu Hu, Xiaoguang Wang","doi":"10.1155/mi/4932970","DOIUrl":"10.1155/mi/4932970","url":null,"abstract":"<p><p>Electroacupuncture (EA) has demonstrated protective effects against hepatic ischemia-reperfusion injury (HIRI) in rat models. This study aimed to explore the underlying molecular mechanisms by which EA exerts its protective effects against HIRI. Gene expression microarray data from the Gene Expression Omnibus (GEO) database were analyzed to identify genes associated with HIRI, followed by differential expression analysis. Our results revealed that EA treatment significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as myeloperoxidase (MPO) activity in liver tissues. Histological analysis indicated decreased necrotic areas and apoptosis in EA-treated liver tissues. Molecular assessments demonstrated that EA downregulated Esr1 expression and inhibited the activation of the TAK1-JNK/p38 signaling pathway, thereby reducing hepatocyte apoptosis and inflammatory responses. These findings suggest that EA serves as a potent therapeutic approach to alleviate HIRI by targeting the Esr1/TAK1-JNK/p38 signaling pathway.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4932970"},"PeriodicalIF":4.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}