Immunobiology最新文献

{"title":"Blue light-emitting diode phototherapy reduces cerebral parasitic load and inflammation in murine congenital toxoplasmosis model","authors":"Débora Nonato Miranda Toledo ,&nbsp;Natiele Carlos ,&nbsp;Giulia Caroline Dantas-Vieira ,&nbsp;Marina Monteiro de Castro Burle ,&nbsp;Lauro de Assis Duarte-Junior ,&nbsp;Maria Laura Cruz Castro ,&nbsp;Talita Rodrigues dos Santos ,&nbsp;Guilherme Paula Costa ,&nbsp;Cristiano Schetini de Azevedo ,&nbsp;Daniela Caldeira Costa ,&nbsp;Élida Mara Leite Rabelo ,&nbsp;Rodrigo Fernando Bianchi ,&nbsp;Érica Santos Martins-Duarte ,&nbsp;André Talvani","doi":"10.1016/j.imbio.2026.153182","DOIUrl":"10.1016/j.imbio.2026.153182","url":null,"abstract":"<div><div>The search for effective therapies to eradicate <em>Toxoplasma gondii</em>, the causative agent of toxoplasmosis, has spanned decades with limited success. Current drugs, including sulfadiazine, spiramycin, and pyrimethamine, face limitations such as parasite resistance, high cellular toxicity, inconsistent efficacy in the acute phase of disease, and the lack of effect in the chronic phase. This study evaluates an innovative adjunctive approach using light-emitting diode phototherapy (BLP) to control <em>T. gondii</em> acute infection during pregnancy. For that, pregnant female Swiss mice (8–9 weeks) were orally infected with 10 cysts of the ME49 strain of <em>T. gondii</em> and exposed to BLP (460 nm, 7 μW/cm2) or conventional white light for 12 h/day over 12 days. After the treatment period, the females were euthanized, and the fetuses, placentas, liver, spleen, maternal brain, and blood were collected for analysis. BLP reduced parasitic load in brain tissue and modulated tissue-specific immune responses, with increased IL-10 in the brain and fetal tissues, elevated CCL2 in liver parenchyma and fetal tissues, and induction of TNF in fetal samples. Serum ferritin and oxidative stress, thiobarbituric acid-reactive substances (TBARS), and superoxide dismutase (SOD) increased in infected mice exposed to BLP, while catalase (CAT) remained unchanged. These findings suggest that BLP exerts both immunomodulatory effects on the infected host and cytotoxicity against <em>T. gondii</em>, supporting its potential as an adjunctive approach for etiological treatment in congenital toxoplasmosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153182"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837418","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":"Integrated single-cell and bulk RNA-seq analysis identifies BCAA metabolism-related prognostic signatures in head and neck squamous cell carcinoma","authors":"Dandan Lu ,&nbsp;Yongjun Liang ,&nbsp;Tao Mo ,&nbsp;Abdeyrim Arikin","doi":"10.1016/j.imbio.2026.153200","DOIUrl":"10.1016/j.imbio.2026.153200","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Impaired metabolism of branched-chain amino acids (BCAAs) has been linked to cancer progression; however, the specific mechanisms underlying BCAA metabolism in head and neck squamous cell carcinoma (HNSCC) remain unclear. This study aimed to identify prognostic genes associated with BCAA metabolism in HNSCC and elucidate their functional roles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;HNSCC-related datasets (TCGA-HNSCC, GSE65858, GSE41613, GSE103322, and GSE140042) were analyzed, and candidate genes were identified by intersecting differentially expressed genes from differential expression analysis with key module genes associated with BCAA metabolism–related gene (BCAA-MRG) scores from weighted gene coexpression network analysis. Prognostic genes were subsequently selected to construct a risk model using univariate Cox regression analysis, proportional hazards testing, and least absolute shrinkage and selection operator regression. Independent prognostic analysis, enrichment analysis, and immune microenvironment assessment were subsequently performed. Moreover, single-cell RNA sequencing (scRNA-seq) and pseudotime analysis were used to evaluate prognostic gene expression at the cellular level. RT-qPCR was used to validate gene expression levels in HNSCC tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;PRDX6&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, and &lt;em&gt;ADA&lt;/em&gt; were identified as prognostic genes for the risk model. The HNSCC samples were stratified into a high-risk group (HRG) and a low-risk group (LRG), with LRG showing notably better survival outcomes. A nomogram model based on risk score and age demonstrated excellent predictive performance for patients with HNSCC. Furthermore, enrichment analysis revealed that the pentose phosphate pathway and fructose and mannose metabolism were substantially associated with HNSCC progression. Differences in the infiltration levels of 20 immune cell types (including plasmacytoid dendritic cells, mast cells, and T follicle helper cells) and the expression of 10 immune checkpoints (such as CD276, CD27, and CD40) were observed between HRG and LRG. Epithelial cells, which exhibited higher expression of prognostic genes, were highlighted as key cells. Notably, the expression trends of these genes varied across different cell differentiation stages. RT-qPCR validation revealed that &lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, and &lt;em&gt;ADA&lt;/em&gt; were highly expressed in the tumor group, whereas &lt;em&gt;PRDX6&lt;/em&gt; showed no significant difference between the tumor and normal tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;A four-gene BCAA metabolism–related signature (&lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;PRDX6&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, &lt;em&gt;ADA&lt;/em&gt;) was identified that stratifies patients with HNSCC into distinct risk groups with different survival and immune microenvironments. The model suggests BCAA–immune interactions, specifically in epithelial cells, provide preliminary insights for prognosis and therapy. Nevertheless, these co","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153200"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211177","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":"High serum uric acid is linked with diabetic kidney disease progression: Evidence from Mendelian randomization analysis and animal study","authors":"Xiaoxian Li ,&nbsp;Yujie Peng ,&nbsp;Wei Zhang ,&nbsp;Yujie Zhao ,&nbsp;Zemei Long ,&nbsp;Lingxi Zhu ,&nbsp;Ting Chen ,&nbsp;Xiao Wei","doi":"10.1016/j.imbio.2026.153199","DOIUrl":"10.1016/j.imbio.2026.153199","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic kidney disease (DKD) is a serious condition associated with diabetes, and the role of uric acid (UA) in its development remains debated.</div></div><div><h3>Methods</h3><div>This study used a Mendelian randomization (MR) analysis, epidemiological validation, transcriptome data mining and animal study to assess the causal relationship between high serum uric acid (HUA) and DKD. Meanwhile, differential expression analysis of lactate-related genes were conducted. Besides, the suggested lactylation associated genes was verified <em>in vivo and vitro</em>. Results: MR shows that gene-predicted serum uric acid level was positively correlated with the risk of DKD (OR = 1.25, 95% CI: 1.01–1.54, <em>P</em> = 0.0396). The finding was further supported by US National Health and Nutrition Survey data. Lactylation associated transcriptome analysis identified associated genes, HMOX1, OGDH, and SPP1. In type 1 and type 2 diabetes HUA mouse model, the expression of HMOX1, OGDH, and SPP1 was significantly enhanced and HUA treatment significantly aggravated renal injury. In podocyte cell line, inhibition of the expression of HMOX1, OGDH, and SPP1 significantly improve the podocyte function.</div></div><div><h3>Conclusions</h3><div>This study provides evidence that high serum uric acid is associated with DKD, and indicates HMOX1, OGDH, and SPP1 as possible important molecules linked to disease progression. These findings offer new biomarkers and potential therapeutic targets for early diagnosis and intervention of DKD.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153199"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148178062","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":"A dual gene-signature framework for glioma survival prediction with multi-cohort validation","authors":"Romeo Macline D'Costa ,&nbsp;Md. Shafiqul Islam ,&nbsp;Md. Masudul Islam","doi":"10.1016/j.imbio.2026.153187","DOIUrl":"10.1016/j.imbio.2026.153187","url":null,"abstract":"<div><div>Despite the proliferation of prognostic gene signatures for glioma, clinical translation remains stalled by poor reproducibility and overfitting. In this study, we address this stability crisis by developing a robust “Dual-Signature Framework” using stability selection—a rigorous resampling method—rather than standard regression. Analyzing RNA-seq data from 1351 patients across the TCGA (<em>n</em> = 694) and CGGA (<em>n</em> = 657) cohorts, we constructed two distinct models. The primary 20-gene “Data-Driven” signature achieved superior predictive accuracy (C-index: 0.7392), significantly outperforming 14 published benchmark models and the current best single-gene predictor (<em>HOXA5</em>). In parallel, we derived a 7-gene “Biology-Driven” signature (including <em>HOXA5</em>, <em>CHI3L1</em>, <em>MMP14</em>) that retained 98% of the predictive power (C-index: 0.7252) while prioritizing mechanistic interpretability. Both models successfully stratified patients into distinct risk groups with high statistical significance (Log-rank <em>p</em> &lt; 0.001) in external validation. Comprehensive subgroup analyses across 19 clinical and molecular subgroups demonstrated robust performance (C-index range: 0.59–0.85), with extended calibration analysis confirming excellent probability estimation (Brier score 0.20 for 5-year predictions). By integrating stability-driven feature selection with biological pathway constraints, this study provides a reproducible, high-performance alternative to unstable “black box” models, offering a translation-ready tool for personalized glioma risk assessment.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153187"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941350","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":"Identification and initial experimental assessment of DCLK3 as a potential sarcopenia biomarker: A multi-omics and machine learning approach","authors":"Jun Zhong ,&nbsp;Jinghong Yang ,&nbsp;Haibo Yang ,&nbsp;Hui Yuan ,&nbsp;Yi Xie ,&nbsp;Xiang Tan ,&nbsp;Zhong Li","doi":"10.1016/j.imbio.2026.153186","DOIUrl":"10.1016/j.imbio.2026.153186","url":null,"abstract":"<div><div>Sarcopenia is an age-related condition marked by high prevalence and significant clinical consequences, underscoring the need for timely diagnostic and predictive strategies. In this study, we applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect gene modules associated with sarcopenia, followed by predictive modeling using machine learning. This methodology aimed to identify robust biomarkers to support early detection and tailored therapeutic strategies. We integrated three sarcopenia-related gene expression datasets from the GEO database. Functional enrichment analysis of differentially expressed genes (DEGs) was performed to interpret their involvement in disease mechanisms. Key modules and hub genes were discerned through WGCNA and machine learning algorithms. Expression patterns of candidate genes were confirmed via RT-qPCR in sarcopenia samples. Gene Set Enrichment Analysis (GSEA) helped uncover signaling pathways linked to DCLK3 expression. Single-nucleus RNA sequencing (snRNA-Seq) was employed to assess transcriptional heterogeneity and cell-cell communication networks during disease progression. Our analysis revealed 472 DEGs and 1325 highly correlated genes from WGCNA. Among 24 overlapping genes, three machine learning approaches—LASSO, Random Forest, and SVM-RFE—converged on DCLK3 as a central biomarker. RT-qPCR confirmed marked dysregulation of DCLK3 in sarcopenia. snRNA-Seq and communication analysis further showed enriched DCLK3 expression in pericytes, with PDGF signaling as the major pathway mediating their crosstalk with other cells. These results position DCLK3 as a compelling diagnostic marker and therapeutic target, providing new insights into sarcopenia pathogenesis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153186"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948170","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":"NEK2 alleviates renal inflammation and apoptosis in sepsis- associated acute kidney injury by activating the MAPK signaling pathway","authors":"Yuchao Shen ,&nbsp;Botao Zhao ,&nbsp;Sumian Dou ,&nbsp;Ling Wang ,&nbsp;Wei Zhang ,&nbsp;Jing Wang ,&nbsp;Chunxue Wu ,&nbsp;Long Yang ,&nbsp;Zhanghai Sun ,&nbsp;Ying Cui","doi":"10.1016/j.imbio.2026.153196","DOIUrl":"10.1016/j.imbio.2026.153196","url":null,"abstract":"<div><div>Sepsis-associated acute kidney injury (S-AKI) has a high mortality rate. Its pathogenesis involves excessive inflammation and cell apoptosis. NEK2 is implicated in the inflammatory process, but its specific role in S-AKI remains unclear. This study investigates the function and mechanism of NEK2 in S-AKI by using a cecal ligation and puncture (CLP)-induced septic mouse model and LPS-treated HK-2 cells to simulate kidney injury in vitro. We found NEK2 was upregulated in the renal cortex of S-AKI mice. Pathological staining indicated vacuolar degeneration and interstitial inflammatory cell infiltration in the kidney, along with local thickening of the basement membrane. Knockdown of NEK2 alleviated kidney damage, reduced serum BUN and Scr levels, and suppressed renal cell apoptosis, as evidenced by decreased Bax and cleaved caspase-3 and increased Bcl2. Furthermore, NEK2 knockdown decreased TNF-α, IL-6, and IL-1β levels in the renal cortex of S-AKI mice. Consistent in vitro results confirmed that NEK2 interference inhibited inflammation and apoptosis. Additionally, we found that NEK2 interacted with ERK2 and increased the levels of p-ERK1/2, exacerbating kidney damage. The protective effect of NEK2 knockdown was counteracted by a p-ERK1/2 agonist. In conclusion, NEK2 is upregulated in S-AKI mice and promotes kidney injury. Mechanistically, NEK2 binds to ERK2, activating the ERK1/2 signaling pathway, which exacerbates cellular inflammation and apoptosis. These findings provide a theoretical basis for understanding S-AKI pathogenesis and hold promise for developing novel therapeutic strategies for patients with this condition.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153196"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224787","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":"A novel mitochondrial-related signature to decode tumor immunity and predict survival in chromophobe renal cell carcinoma","authors":"Shuting Huang ,&nbsp;Congcong Dai ,&nbsp;Xia Li ,&nbsp;Zuosen Liao ,&nbsp;Suwan Mu ,&nbsp;Zhonghua Wen ,&nbsp;Liandong Wei ,&nbsp;Liang Zhong ,&nbsp;Liuqing Wei ,&nbsp;Miaoling Wei ,&nbsp;Jun Ou ,&nbsp;Yong Li","doi":"10.1016/j.imbio.2026.153191","DOIUrl":"10.1016/j.imbio.2026.153191","url":null,"abstract":"<div><div>Chromophobe renal cell carcinoma (chRCC) comprises about 5%–10% of all renal cancer cases, some of which are aggressive and metastatic. Mitochondria are significantly activated in chRCC, however, a risk model based on mitochondrial-related genes for chRCC has not been constructed to date. We constructed a novel mitochondrial-related risk model consisting of <em>TIMM8A</em>, <em>RECQL4</em>, <em>MTERF1</em>, and <em>DUS2</em>. Our model highlighted distinct immune infiltration patterns between the different risk groups. Moreover, the TME signature genes and immune regulatory factors were significantly associated with the risk scores. Combining the risk score with immune/stromal score and TMB can improve the accuracy of the risk model in patient stratification and prognosis prediction. Notably, our computational analysis based on GDSC's pRRophetic algorithm suggests that LCL161 and UMI-77 may be more effective in the low-risk group, while sapitinib and luminespib show potential efficacy in the high-risk group. In conclusion, our study indicates this model holds high promise as a reliable biomarker for outcome prediction and precision-medicine stratification in chRCC patients.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153191"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972270","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":"Comprehensive pan-cancer analysis of HSPA1B as a biomarker for prognosis and immunity","authors":"Xiyao Wang ,&nbsp;Ting Wang ,&nbsp;Xuanzhe Wang ,&nbsp;Fuyan Lv ,&nbsp;Xiaohua Han ,&nbsp;Bixiao Cao ,&nbsp;Xiang Ma ,&nbsp;Peng Sun","doi":"10.1016/j.imbio.2026.153195","DOIUrl":"10.1016/j.imbio.2026.153195","url":null,"abstract":"<div><div>HSPA1B, a member of the HSP70 family, functions as a molecular chaperone essential for protein folding and stress responses. Emerging evidence indicates that HSPA1B is overexpressed in multiple cancers and contributes to tumor progression and immune modulation. However, its comprehensive role across cancer types remains unclear. To determine whether HSPA1B could serve as a universal biomarker, we performed an integrative pan-cancer analysis to investigate its expression, regulation, and function. Results demonstrate that HSPA1B is significantly upregulated across multiple cancers and strongly associated with poor prognosis. Genomic analyses reveal that gene amplification is the predominant driver of its overexpression, which is further linked to increased genomic instability. Epigenetic regulation contributes to HSPA1B expression, as evidenced by its inverse correlation with DNA methylation levels. Notably, HSPA1B expression is positively associated with cancer-associated fibroblast infiltration and negatively with CD8⁺ T cell abundance, indicating its role in establishing an immunosuppressive tumor microenvironment. We further selected cholangiocarcinoma (CHOL) as a model due to its high HSPA1B expression and limited treatment options, and found that HSPA1B contributes to chemotherapy resistance and malignant phenotypes. Collectively, this study identifies HSPA1B as a pan-cancer oncogenic driver and positions it as a promising predictive biomarker and therapeutic target.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153195"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224789","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":"Estrogen ameliorates Caerulein-induced inflammatory injuries and oxidative stress in acute pancreatitis via STAT3/PGAM1 signaling","authors":"Weixi Shan,&nbsp;Wenyu Zhou,&nbsp;Ya Huang,&nbsp;Hengyang Ou,&nbsp;Long Yang","doi":"10.1016/j.imbio.2026.153177","DOIUrl":"10.1016/j.imbio.2026.153177","url":null,"abstract":"<div><h3>Background</h3><div>Acute pancreatitis (AP) is an acute inflammatory abdominal disease frequently associated with intestinal barrier dysfunction. The steroid hormone 17β-estradiol is an estrogen that exhibits anti-inflammatory effects in various inflammatory diseases. However, its potential beneficial effects on AP and the underlying mechanism have not been investigated.</div></div><div><h3>Methods</h3><div>57 patients with AP and 30 healthy volunteers were enrolled in this study. Caerulein-induced human pancreatic duct epithelial (HPDE) cells were used to establish an in vitro research model. Phosphoglycerate mutase 1 (PGAM1) and Signal transducer and activator of transcription 3 (STAT3) were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels were analyzed using ELISA kits and RT-qPCR assay. Reactive oxygen species (ROS), malondialdehyde (MDA), Superoxide dismutase (SOD), and Catalase (CAT) products were detected using special assay kits. Following JASPAR prediction, the binding between STAT3 and the PGAM1 promoter was verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The effects of 17β-estradiol, STAT3, and PGAM1 on Caerulein-induced HPDE cell damage were assessed. The impacts of 17β-estradiol and STAT3 on pancreatic injury in Caerulein-induced AP mouse model.</div></div><div><h3>Results</h3><div>PGAM1 and STAT3 were highly expressed in AP patients and Caerulein-treated HPDE cells. PGAM1 silencing alleviated Caerulein-triggered HPDE cell inflammatory injury and oxidative stress. Mechanistically, STAT3 was a transcription factor of PGAM1 that promoted PGAM1 transcription by directly binding to its promoter region. 17β-estradiol repressed Caerulein-caused HPDE cell inflammatory injury and oxidative stress by regulating the STAT3/PGAM1. In addition, 17β-estradiol treatment attenuated pancreatic injury in cerulein-induced AP mice by regulating STAT3.</div></div><div><h3>Conclusion</h3><div>17β-estradiol treatment blocked Caerulein-induced HPDE cell inflammatory injury and oxidative stress by targeting the STAT3/PGAM1 axis, providing a promising strategy to protect against AP.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153177"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770166","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":"Comprehensive bioinformatic and experimental approaches to analyze miR-200a, miR-1, and miR-548-3p expression and their targeted oxidative stress and glucose metabolic related hub genes in rheumatoid arthritis","authors":"B. Alzahrani ,&nbsp;B. Rauff ,&nbsp;M.R. Chaudhry ,&nbsp;M.S. Hakim ,&nbsp;Y. Ishaq ,&nbsp;I. Amjad ,&nbsp;A. Yousuf ,&nbsp;S.A. Chudhary ,&nbsp;A. Ikram","doi":"10.1016/j.imbio.2026.153201","DOIUrl":"10.1016/j.imbio.2026.153201","url":null,"abstract":"<div><div>Rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent synovial inflammation, oxidative stress, and metabolic reprogramming. Emerging evidence highlights miRNAs as key post-transcriptional regulators linking these pathogenic processes. Among them, miR-200a, miR-1, and miR-548-3p have been implicated in oxidative stress responses and glucose metabolism; however, their roles in RA remain largely unexplored. This study integrates bioinformatic prediction and experimental validation to examine the expression profiles of these miRNAs, identify their target genes related to oxidative stress and metabolism, and elucidate their contribution to RA pathogenesis. RT-PCR analysis revealed significant upregulation of miR-200a and downregulation of miR-1 and miR-548-3p in RA patients. RA-associated DEGs were identified from publicly available GEO microarray datasets. Further, genes linked to oxidative stress and glucose metabolism were retrieved from GeneCards and MSigDB. Overlapping genes across datasets were subjected to GO and KEGG enrichment analyses, followed by the construction of a PPI network using STRING. Five hub genes—MAPK1, FOXP1, CDC42, RUNX1, and ETS1—were identified as central nodes within the PPI network. Functional enrichment indicated their involvement in myeloid cell differentiation, regulation of apoptosis, and peptidyl-tyrosine phosphorylation, while KEGG mapping associated them with cellular senescence, circadian rhythm pathways, viral carcinogenesis, and neurotrophins signaling. Collectively, these findings suggest that miR-200a, miR-1, and miR-548-3p potentially involved in oxidative and metabolic pathways in RA, offering candidate biomarkers and therapeutic targets for disease management. Further, RT-PCR for hub genes showed elevated expression of RUNX1, MAPK1, ETS1, FOXP1, and CDC42 in RA patients. Overall, our findings reveal a potential miRNA-mediated regulatory axis underlying oxidative and metabolic disturbances in RA, offering new insights into disease mechanisms and laying the groundwork for the development of novel biomarkers and therapeutic targets.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153201"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204711","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}