{"title":"Retraction notice to \"Cyanorona-20: The first potent anti-SARS-CoV-2 agent\" [Int. Immunopharmacol. 98 (2021) 107831].","authors":"Amgad M Rabie","doi":"10.1016/j.intimp.2025.114980","DOIUrl":"10.1016/j.intimp.2025.114980","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"114980"},"PeriodicalIF":4.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonietta Rizzo, Rossella Paolillo, Elisabetta Buommino, Alfonso Galeota Lanza, Luigi Guida, Marco Annunziata, Caterina Romano Carratelli
{"title":"Retraction notice to \"Modulation of cytokine and β-defensin 2 expressions in human gingival fibroblasts infected with Chlamydia pneumoniae\" [Int. Immunopharmacol. 8(9) (2008) 1239-1247].","authors":"Antonietta Rizzo, Rossella Paolillo, Elisabetta Buommino, Alfonso Galeota Lanza, Luigi Guida, Marco Annunziata, Caterina Romano Carratelli","doi":"10.1016/j.intimp.2025.114981","DOIUrl":"10.1016/j.intimp.2025.114981","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"114981"},"PeriodicalIF":4.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Ma , Zhibin Lan , Yang Yang , Rui Sun , Di Xue , Xue Lin , Yajing Su , Long Ma , Zhijun Hu , Gang Wu , Xiaoxin He , Kuanmin Tian , Qunhua Jin
{"title":"Calreticulin-driven immunogenic cell death promotes osteoclast differentiation and osteoarthritis progression via the LRP1/Rac1 signaling","authors":"Qi Ma , Zhibin Lan , Yang Yang , Rui Sun , Di Xue , Xue Lin , Yajing Su , Long Ma , Zhijun Hu , Gang Wu , Xiaoxin He , Kuanmin Tian , Qunhua Jin","doi":"10.1016/j.intimp.2025.115277","DOIUrl":"10.1016/j.intimp.2025.115277","url":null,"abstract":"<div><div>Aberrant osteoclast activation in subchondral bone is a hallmark of osteoarthritis (OA). This study identifies calreticulin (CALR), a key immunogenic cell death (ICD) marker, as a critical regulator of osteoclast differentiation and OA pathogenesis. Proteomic analysis revealed elevated CALR expression in subchondral bone from OA patients, which was further validated in human specimens and a destabilization of the medial meniscus (DMM)-induced murine OA model. In vitro, CALR upregulation during osteoclast differentiation activated the low-density lipoprotein receptor-related protein 1 (LRP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling pathway, promoting osteoclastogenesis and bone resorption. These effects were suppressed by the apoptosis inhibitor zVAD-fmk or CALR knockdown. CALR-deficient mice exhibited attenuated subchondral bone damage and delayed OA progression post-DMM. Mechanistically, CALR governs osteoclast function via LRP1/Rac1-mediated nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) activation and secretion of bone-resorbing factors (matrix metalloproteinase-9 (MMP-9), cathepsin K (CTSK)). Our study establishes CALR as a novel therapeutic target for OA, bridging ICD to osteoclast-driven subchondral bone resorption and microarchitectural disruption.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115277"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moran Wang , Bowen Ren , Xiaofan Wu , Junyi Guo , Yu Cao , Lintong Men , Wei Shi , Cuntai Zhang , Li Lin , Jiagao Lv , Sheng Li , Shengqi Huo
{"title":"S100A9 inhibition ameliorates HFpEF by modulating mitochondrial fission and oxidative stress","authors":"Moran Wang , Bowen Ren , Xiaofan Wu , Junyi Guo , Yu Cao , Lintong Men , Wei Shi , Cuntai Zhang , Li Lin , Jiagao Lv , Sheng Li , Shengqi Huo","doi":"10.1016/j.intimp.2025.115280","DOIUrl":"10.1016/j.intimp.2025.115280","url":null,"abstract":"<div><div>Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and myocardial stiffness, with limited treatment options due to the unclear molecular mechanisms underlying the disease. In this study, we investigate the role of S100A9, an inflammatory mediator, in regulating mitochondrial dynamics in HFpEF. Using “two-hit” (high-fat diet and L-NAME) and db/db mouse models, we show that S100A9 is significantly elevated in both cardiac tissue and serum, correlating with impaired diastolic function, cardiac hypertrophy, and increased oxidative stress. Inhibition of S100A9 with Paquinimod (PAQ) improved diastolic function, reduced cardiac hypertrophy, and decreased S100A9-positive macrophage infiltration, while preventing M1 macrophage polarization. In vitro, S100A9 secreted by palmitic acid-stimulated RAW 264.7 macrophages promoted mitochondrial fission in AC16 cardiomyocytes by increasing p-Drp1 and Fis1 expression, similar to the effects observed with recombinant S100A9. Excessive mitochondrial fission, regulated by S100A9, is a key factor in HFpEF progression. Transcriptomic analysis revealed significant upregulation of pyruvate dehydrogenase kinase 4 (PDK4) in HFpEF mice. Mechanistically, S100A9 induced PDK4 expression via SPI1-mediated transcription, exacerbating oxidative stress and mitochondrial fragmentation. PAQ treatment or silencing PDK4/SPI1 in AC16 cells reversed these effects, restoring ATP levels and stabilizing mitochondrial membrane potential. Cardiomyocyte-specific PDK4 knockdown in vivo further ameliorated HFpEF progression without affecting systolic function. These findings highlight S100A9 inhibition as a promising therapeutic strategy for HFpEF by targeting mitochondrial dysfunction through the S100A9/SPI1/PDK4 axis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115280"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dalia H.H. Amer , Mai F. Tolba , Maha R.A. Abdollah
{"title":"In vivo modulation of the tumor microenvironment: anti-tumor effects of combination therapy of fucoidan and small molecule immune checkpoint inhibitor BMS-202","authors":"Dalia H.H. Amer , Mai F. Tolba , Maha R.A. Abdollah","doi":"10.1016/j.intimp.2025.115271","DOIUrl":"10.1016/j.intimp.2025.115271","url":null,"abstract":"<div><div>Cancer immunotherapy has gained significant momentum, particularly in counteracting the immunosuppressive tumor microenvironment (TME). This study investigates the therapeutic potential of a combination therapy of fucoidan, a marine-derived polysaccharide with anti-cancer and immunomodulatory properties, and BMS-202, a small molecule immune checkpoint inhibitor targeting programmed cell death 1 (PD-1) and its ligand PDL-1, in a murine model of Ehrlich solid-phase carcinoma. Tumor bearing mice received saline (control), BMS-202, fucoidan or their combination (at half the monotherapy doses). Both monotherapies significantly reduced tumor volumes. Histological analysis of excised tumors from the control group revealed large areas of viable tumor cells, whereas the combination therapy induced central tumor necrosis, with abundant pyknotic and fragmented tumor cells. The area percentage of tumor necrosis increased by 6.3-, 4.1- and 1.4-fold in the combination group versus control, fucoidan, and BMS-202, respectively (<em>p</em> < 0.05). Immunohistochemistry (IHC) was used to assess Ki-67 and cleaved caspase-3, ELISA measured IL-6 and TGF-β while Western blotting evaluated p-ERK1/2, p-Akt, and p-p38 MAPK. The combination therapy significantly increased cleaved caspase-3 by 8.3 folds and reduced Ki-67, IL-6, TGF-β, p-ERK1/2, p-Akt, and p-p38 MAPK levels by 67 %, 98.9 %, 75.8 %, 69 %, 85 %, and 87.5 %, respectively, relative to the control (<em>p</em> < 0.05). Additionally, immune profiling of the tumor tissue using IHC revealed an increased CD8+/FOXP3+ ratio and a reduced CD4+/CD8+ ratio, suggesting an immunomodulatory effect. In conclusion, fucoidan demonstrated the potential to enhance the anti-tumor efficacy of BMS-202 via modulation of the immune TME and downregulating key oncogenic pathways, warranting further investigation into its role in combination with immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115271"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saiqun Nie, Li Fang, Bingbin Wang, Ran Chen, Tao Wei, Yanren Zhang, Hao Ji, Yanqing Wu
{"title":"ZEB2: a multifunctional regulator of neural injury repair","authors":"Saiqun Nie, Li Fang, Bingbin Wang, Ran Chen, Tao Wei, Yanren Zhang, Hao Ji, Yanqing Wu","doi":"10.1016/j.intimp.2025.115266","DOIUrl":"10.1016/j.intimp.2025.115266","url":null,"abstract":"<div><div>Nerve injury is a pathological condition characterized by damage or necrosis of nerve cells in injured areas due to trauma, infection, ischemia, genetic factor or other factors. Neural injury repair is precisely regulated by the complex regulatory network of body. Zinc finger E-box-binding protein 2 (ZEB2), known as a critical transcription factor, not only serves as a key participant in embryonic neural development, but also exerts a vital regulatory role in neural injury repair. This paper summarizes the structure, function, and regulatory network of ZEB2 and then elucidates its pivotal roles in glial scar formation, remyelination, and epithelial-to-mesenchymal transition (EMT) for neural injury repair. Furthermore, it provides a comprehensive summary of advances about ZEB2's regulatory role in peripheral nerve injury, spinal cord injury, hemorrhagic brain injury, and Mowat-Wilson syndrome. This paper deepens the theoretical significance of ZEB2 in regulating neural injury repair and aims to offer a new perspective for therapeutic strategies in neural injury repair.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115266"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang Liu , Rong Huang , Qin Wang , Ruitao Wang , Jia Lu , Yanying Zhang , Xuejiao Ma , Xiaoyu Liu , Xudong Kong , Pengmei Li , Liqun Jia , Yanni Lou
{"title":"Leveraging readily available clinical data with machine learning to predict first-line immunotherapy outcomes in non-small cell lung cancer","authors":"Fang Liu , Rong Huang , Qin Wang , Ruitao Wang , Jia Lu , Yanying Zhang , Xuejiao Ma , Xiaoyu Liu , Xudong Kong , Pengmei Li , Liqun Jia , Yanni Lou","doi":"10.1016/j.intimp.2025.115259","DOIUrl":"10.1016/j.intimp.2025.115259","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) are essential first-line treatments for recurrent or metastatic non-small cell lung cancer (NSCLC). However, predicting their effectiveness and the occurrence of immunotherapy-related adverse events (irAEs) remains challenging.</div></div><div><h3>Methods</h3><div>This retrospective study involved NSCLC patients who received first-line ICI therapy at China-Japan Friendship Hospital in Beijing, China, between October 29, 2018, and July 10, 2024. We employed five machine learning models to predict treatment responses to ICIs and the occurrence of irAEs.</div></div><div><h3>Results</h3><div>A total of 397 NSCLC patients who received first-line ICIs were included in the analysis, with 277 patients in the train-validation cohort and 120 in the test cohort. The neural network and gradient boosting models were the most effective for predicting treatment responses, achieving AUC values of 0.87 and 0.84, respectively. For predicting irAEs, random forest and gradient boosting emerged as the top performers, with AUC values of 0.84 and 0.80. Feature importance analysis identified key predictors such as red blood cell (RBC) counts and metastatic sites for treatment response, while metastatic sites and sex were significant for irAE prediction. In the validation cohort, the neural network demonstrated strong performance in predicting treatment response (AUC of 0.84, recall of 0.8406, and F1 score of 0.8007), while the random forest model excelled in predicting irAEs (AUC of 0.82, accuracy of 0.7417, precision of 0.7500, recall of 0.8261, and F1 score of 0.7862).</div></div><div><h3>Conclusion</h3><div>These findings highlight the potential for enhancing personalized treatment strategies for NSCLC patients undergoing first-line ICI therapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115259"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}