International immunopharmacology最新文献

{"title":"Ginsenoside CK regulates non-alcoholic fatty liver disease by regulating liver fat metabolism and gut microbiota","authors":"Yifang Xiong ,&nbsp;Chenhui Zhu ,&nbsp;Yanru Chen ,&nbsp;Ru Xu ,&nbsp;Rongzhan Fu ,&nbsp;Xiaoxuan Ma ,&nbsp;Zhiguang Duan","doi":"10.1016/j.intimp.2026.116338","DOIUrl":"10.1016/j.intimp.2026.116338","url":null,"abstract":"<div><div>The global incidence of non-alcoholic fatty liver disease (NAFLD) is on a continuous rise, characterized by hepatic lipid metabolism disorder and gut microbiota dysbiosis. Although ginsenoside compound K (CK) exhibits hepatoprotective and anti-inflammatory activities, its specific role in the pathogenesis of NAFLD remains to be fully elucidated. In this study, a high-fat-high-cholesterol (HFHC) diet-induced NAFLD mouse model was used to investigate the protective effects of CK against the disease. The results demonstrated that CK intervention significantly attenuated HFHC diet-induced body weight gain in mice: the body weight of mice in the CK-L group (60 mg/kg) decreased by approximately 11.7%, hepatic inflammation was reduced by about 35%–45%, and lipid deposition was improved by roughly 50%–60%. Mechanistically, CK activates the peroxisome proliferator-activated receptor (PPAR) signaling pathway, regulates the expression of lipid metabolism-related genes and proteins, thereby ameliorating lipid metabolism disorder. Meanwhile, CK reverses HFHC diet-induced gut microbiota dysbiosis, upregulates the abundance of the beneficial bacterium Akkermansia, and modulates the intestinal phylum composition in NAFLD mice by increasing the proportion of Bacteroidetes and decreasing that of Firmicutes. CK regulates the occurrence and development of NAFLD via the gut-liver axis, providing experimental evidence for subsequent mechanistic research on NAFLD prevention and treatment as well as the exploration of candidate drugs.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116338"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192731","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}

{"title":"Necroptosis mediated by FKBP5 in alveolar fibroblasts drives Pseudomonas aeruginosa-induced acute lung injury","authors":"Dong Zhang ,&nbsp;Yinghui Qu ,&nbsp;Yuexin Han ,&nbsp;Wei Liu ,&nbsp;Xiaozhi Wang ,&nbsp;Tao Wang ,&nbsp;Qian Qi","doi":"10.1016/j.intimp.2026.116368","DOIUrl":"10.1016/j.intimp.2026.116368","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> (PA) is a leading cause of nosocomial infections and is frequently associated with severe dysregulation of the pulmonary inflammatory microenvironment. Alveolar fibroblasts can regulate the inflammatory microenvironment, but their specific role in PA-induced lung injury remains elusive. Using single-cell RNA sequencing, we identified a pro-inflammatory phenotype in fibroblasts during PA-induced acute lung injury, which was associated with high expression of the inflammatory target FK506 binding protein 51 (FKBP5). FKBP5 deficiency markedly alleviated inflammation and pulmonary edema in <em>Fkbp5</em>^−/− mice with bacterial lung injury. Consistently, single-cell RNA sequencing revealed that FKBP5 deficiency attenuated the pro-inflammatory phenotype of fibroblasts. Furthermore, alveolar fibroblast-specific conditional knockout of FKBP5 confirmed the critical contribution of FKBP5 in these cells to PA-induced inflammatory injury. Mechanistically, FKBP5 promoted necroptosis in alveolar fibroblasts, thereby activating NF-κB signaling, and driving neutrophil recruitment and activation, which collectively exacerbated lung injury. These findings identify FKBP5-mediated necroptosis in alveolar fibroblasts as a central mechanism of PA-associated acute lung injury and suggest FKBP5 as a promising therapeutic target.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116368"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192735","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}

{"title":"miR-107-5p mitigates spinal cord injury by targeting the PLOD2/HK2 axis","authors":"Mengqiu Deng ,&nbsp;Guowei Jiang ,&nbsp;Kesheng Huang ,&nbsp;Shaowei Li ,&nbsp;Yun Xia ,&nbsp;Zhiwei Cao ,&nbsp;Wei Chen ,&nbsp;Ruifeng Ding","doi":"10.1016/j.intimp.2026.116355","DOIUrl":"10.1016/j.intimp.2026.116355","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) induces persistent neuroinflammation and metabolic disturbances that contribute to neuropathic pain and neuronal damage. Although microRNAs are involved in these processes, their regulatory roles remain incompletely understood. This study aimed to identify miRNA-associated metabolic regulators linking glycolytic alterations with neuroinflammatory responses after SCI.</div></div><div><h3>Methods</h3><div>A contusion-induced mouse SCI model was used to assess behavioral sensitivity, motor function, and histological, molecular, and ultrastructural changes. Transcriptomic and microRNA profiling were performed to identify candidate regulators. Functional validation of miR-107-5p was conducted in BV-2 microglia and in vivo through overexpression studies, focusing on metabolic activity, microglial polarization, and cell death–related pathways.</div></div><div><h3>Results</h3><div>SCI reduced pain thresholds and motor performance and induced neuronal injury, mitochondrial abnormalities, and pro-inflammatory microglial activation. Transcriptomic analysis revealed sustained upregulation of the glycolytic regulators PLOD2 and HK2. Integrative profiling identified miR-107-5p as a potential upstream regulator of PLOD2. Overexpression of miR-107-5p in vitro and in vivo decreased PLOD2 and HK2 expression, reduced glycolytic activity, and attenuated inflammatory and apoptotic responses. These effects were diminished following PLOD2 knockdown, suggesting a PLOD2-dependent mechanism. Intrathecal administration of miR-107-5p in SCI mice was associated with higher pain thresholds, better motor performance, and reduced markers of neuroinflammation and neural injury.</div></div><div><h3>Conclusions</h3><div>miR-107-5p modulates glycolytic metabolism and inflammatory signaling after SCI, in part through regulation of the PLOD2/HK2 pathway. These findings provide mechanistic insight into miRNA-mediated metabolic regulation in SCI and support further investigation of miR-107-5p in the context of post-injury neuroinflammation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116355"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179498","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}

{"title":"Thrombospondin-1-mediated macrophage efferocytosis dysfunction exacerbates intestinal pathology in Hirschsprung's disease","authors":"Qiuling Li ,&nbsp;Hanyi Kong ,&nbsp;Qijun Li ,&nbsp;Tingwei Chen ,&nbsp;Lei Chen ,&nbsp;Fan Wang ,&nbsp;Xinyu Zhang ,&nbsp;Yijun Wu ,&nbsp;Yu Zhu ,&nbsp;Zhi Geng ,&nbsp;Jiajia Zou ,&nbsp;Yan Chen ,&nbsp;Jun Liu ,&nbsp;Shungen Huang","doi":"10.1016/j.intimp.2026.116344","DOIUrl":"10.1016/j.intimp.2026.116344","url":null,"abstract":"<div><h3>Background</h3><div>Hirschsprung's disease (HSCR) is a prevalent pediatric congenital enteropathy characterized by disrupted intestinal homeostasis, persistent inflammation, and progressive intestinal fibrosis. However, the cellular and molecular mechanisms underpinning these pathological hallmarks remain incompletely elucidated. Given the pivotal role of macrophages in inflammation resolution and tissue repair, and the established function of thrombospondin-1 (THBS1) in regulating macrophage polarization and efferocytosis, we focused on THBS1 to dissect the mechanisms of HSCR-associated pathology.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) was performed on 3 paired colon biopsies of aganglionic HSCR lesions and proximal ganglionic controls. Inflammation and fibrosis markers were assessed in additional HSCR samples (<em>n</em> = 5) by histopathology, qRT-PCR, and immunofluorescence. Macrophage efferocytosis was quantified by flow cytometry and immunofluorescence. Mechanistic studies employed recombinant THBS1 (rTHBS1), siRNA/lentiviral transduction, CD36 inhibition, and Rac1 FRET biosensors in bone marrow-derived macrophages (BMDMs), with in vivo confirmation in DSS-induced colitis.</div></div><div><h3>Results</h3><div>scRNA-seq revealed stromal-specific THBS1 downregulation in HSCR as a top candidate regulator of dysregulated macrophage function. HSCR macrophages exhibited proinflammatory hyperactivation and impaired pro-resolving polarization with reduction of CD206⁺ proportion and downregulation of TGFB1. Mechanistically, THBS1 sustains intestinal homeostasis by mediating macrophage pro-resolving functions and enhances efferocytosis via activation of the CD36/Rac1 signaling axis. Inhibition of THBS1 abrogates macrophage efferocytosis by appropriate 50%, leading to unresolved inflammation and intestinal fibrosis. Critically, rTHBS1 treatment rescued efferocytosis in THBS1-deficient BMDMs. Notably, impaired macrophage THBS1 signaling was consistently observed in human HSCR specimens.</div></div><div><h3>Conclusion</h3><div>This study identifies stromal THBS1-CD36/Rac1 signaling as a critical regulator of macrophage efferocytosis and resolution in HSCR. THBS1 deficiency drives persistent post-surgical inflammation and fibrosis, establishing it as a novel therapeutic target and potential biomarker for precision interventions to improve long-term outcomes in this pediatric disorder.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116344"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179491","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}

{"title":"Distinct roles of PINK1 autophosphorylation in neonatal hypoxia with or without convulsions","authors":"Yujie Zhai ,&nbsp;Xiaoqian Wang ,&nbsp;Hua Zhou,&nbsp;Yunrong Zhang,&nbsp;Qiaoyun Wang,&nbsp;Wenxiao Cao,&nbsp;Mengshuang Liu,&nbsp;Anqing Gao,&nbsp;Hongliu Sun","doi":"10.1016/j.intimp.2026.116343","DOIUrl":"10.1016/j.intimp.2026.116343","url":null,"abstract":"<div><div>This study explored the distinct roles of PINK1 in neonatal hypoxia with and without convulsions. Various models of hypoxia with different severities have been established using neonatal C57BL/6 J mice. In addition, short hairpin RNA (shRNA) interventions targeting translocase of the outer mitochondrial membrane 7 or mitochondrial ATPase associated with diverse cellular activities, such as protease 1 homolog, inhibitor, and promoter of PINK1 autophosphorylation, were administered to modulate PINK1 activity levels. After exposure to severe hypoxia (15 min) that induced convulsions, phosphorylated PINK1 levels increased, accompanied by enhanced mitophagy, increased mitochondrial reactive oxygen species, neuronal damage and elevated epileptic susceptibility. Moreover, inhibition of PINK1 phosphorylation alleviates oxidative stress injury and reduces epileptic susceptibility, whereas enhancement of PINK1 phosphorylation aggravates oxidative stress damage. PINK1-induced mitophagy and oxidative stress injury were also elevated following mild hypoxia (130 s), without convulsions. However, unlike the 15-min hypoxic condition, either increasing or suppressing PINK1 phosphorylation via shRNA intervention exacerbated hypoxia-induced injury. These findings suggest that excessive phosphorylated PINK1 levels following severe hypoxia with convulsions, promote neuronal injury and increase epileptic susceptibility. In contrast, moderate PINK1 phosphorylation, induced by mild hypoxia without convulsions, exerts neuroprotective effects. Overall, this study elucidates the dual roles of PINK1 autophosphorylation in neonatal hypoxia with and without convulsions, and provides a theoretical basis for the therapeutic modulation of PINK1 activity in neonatal hypoxia.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116343"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157087","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}

{"title":"NGR-modified cancer-associated fibroblast-derived exosomes deliver resveratrol to inhibit CXCR2/NF-κB signaling in myeloid-derived suppressor cells and reverse immune suppression in liver cancer","authors":"Lijuan Ding ,&nbsp;Qiang Wang ,&nbsp;Xue Wang ,&nbsp;Weijia Fu ,&nbsp;Chen Deng ,&nbsp;Shudong Wang","doi":"10.1016/j.intimp.2026.116326","DOIUrl":"10.1016/j.intimp.2026.116326","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to develop NGR (Asn-Gly-Arg) peptide–modified cancer-associated fibroblast (CAF)-derived exosomes for resveratrol delivery (NGR-Exos@Res) to target myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By inhibiting the CXCR2/NF-κB pathway, this strategy reprograms MDSC function, reverses immune suppression, restores CD8⁺ T-cell antitumor activity, and suppresses liver cancer (LC) progression.</div></div><div><h3>Methods</h3><div>Network pharmacology and molecular docking identified CXCR2 as a key Res target. Public scRNA-seq data analyzed MDSC-T-cell interactions in LC. Bone marrow-derived MDSCs were treated with Res <em>in vitro</em>; effects on CXCR2/immunosuppressive molecules were assessed <em>via</em> Western blot/immunofluorescence. A CAF line expressing 3×His-NGR-CD63 was generated to produce NGR-Exos loaded with Res (NGR-Exos@Res). Their toxicity, uptake, and biodistribution were evaluated. Efficacy was tested in a murine LC xenograft model, assessing MDSC function, T-cell activation, and immune evasion.</div></div><div><h3>Results</h3><div>Single-cell transcriptomic analysis revealed that CXCR2 was highly expressed in MDSCs within HCC tissues. Moreover, inhibitory ligand–receptor pairs such as MIF–(CD74⁺CXCR4) were significantly activated in the interaction network between MDSCs and T cells. <em>In vitro</em> experiments demonstrated that resveratrol markedly downregulated the expression of CXCR2, Arg-1, and iNOS in MDSCs, thereby suppressing their proliferation while enhancing CD8⁺ T-cell proliferation and IFN-γ secretion. The successfully constructed NGR-Exos@Res drug delivery system exhibited a drug encapsulation efficiency of 19.3% and improved serum stability. <em>In vivo</em>, treatment with NGR-Exos@Res significantly reduced tumor volume, inhibited the CXCR2/NF-κB signaling pathway, decreased the proportion of MDSCs, and enhanced CD8⁺ T-cell activity.</div></div><div><h3>Conclusion</h3><div>In this study, we successfully constructed NGR peptide-modified Exos derived from CAFs for the targeted delivery of Res. This work innovatively proposes a novel immunotherapeutic strategy that targets tumor-associated MDSCs rather than directly killing tumor cells. Mechanistically, we identify and validate CXCR2 as a previously unrecognized functional target of resveratrol in MDSCs, through which resveratrol suppresses NF-κB signaling and reprograms MDSC function. Collectively, NGR-Exos@Res represents a precise and efficient delivery platform capable of reversing the immunosuppressive microenvironment in LC and provides a promising combinatorial strategy to overcome immunotherapy resistance by targeting immunosuppressive myeloid cells.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116326"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179431","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}

{"title":"Allicin protects against inflammation via suppression of PI3K/AKT/NF-κB signaling pathway in the model of acute cutaneous injury mouse and LPS-induced keratinocyte","authors":"Haohong Zheng,&nbsp;Diandong Tang,&nbsp;Shuaihao An,&nbsp;Li Fang,&nbsp;Jian Li,&nbsp;Qiangqiang Zhang,&nbsp;Jundong Kong,&nbsp;Wei Lu,&nbsp;Zhongkai Fan","doi":"10.1016/j.intimp.2026.116331","DOIUrl":"10.1016/j.intimp.2026.116331","url":null,"abstract":"<div><h3>Background</h3><div>Wound healing is crucial for tissue repair, with inflammatory regulation being a key determinant of recovery. While Allicin exhibits multifunctional therapeutic properties, its mechanistic basis for anti-inflammatory protection during wound healing requires elucidation.</div></div><div><h3>Methods</h3><div>In vitro, we established an inflammatory model by stimulating HaCaT cells with lipopolysaccharide (LPS). In vivo, experiments employed a standardized full-thickness excisional wound model (1 cm diameter) in mice. Cellular responses were evaluated using CCK-8 assays and scratch tests. Protein expression of inflammatory markers (IL-6, TNF-α), proliferative indicators (PCNA), and PI3K/AKT/NF-κB pathway components (including phosphorylation status) were analyzed through western blotting and immunofluorescence. Pathway specificity was confirmed via PI3K inhibitor (LY294002) pretreatment. Tissue morphology and collagen deposition were assessed using hematoxylin-eosin (H&amp;E) and Masson's trichrome staining.</div></div><div><h3>Results</h3><div>In vitro, Allicin dose-dependently suppressed HaCaT cell within 24 h, regardless of LPS stimulation. In vivo, Allicin treatment significantly enhanced wound closure rates (<em>P</em> &lt; 0.05) and promoted collagen deposition and re-epithelialization. Significantly reduced protein levels of IL-6, TNF-α, PCNA, PI3K, AKT, and NF-κB (including phosphorylation status) were observed in Allicin group versus LPS-treated group or Injury group (<em>P</em> &lt; 0.05) in both Western blotting and immunofluorescence.</div></div><div><h3>Conclusion</h3><div>Allicin accelerates wound healing by modulating PI3K/AKT/NF-κB signaling to suppress inflammation and abnormal proliferation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116331"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179493","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}

{"title":"Periostin ameliorates impaired osteogenic differentiation of bone marrow mesenchymal stem cells from T2DM rats via modulating autophagy and cellular senescence","authors":"Yanling Mi ,&nbsp;Danni Wei ,&nbsp;Bingli Du ,&nbsp;Jiani Wang ,&nbsp;Jin Qi ,&nbsp;Ran Zhang ,&nbsp;Liling Du ,&nbsp;Juan Ren ,&nbsp;Bing Li ,&nbsp;Xiuping Wu","doi":"10.1016/j.intimp.2026.116340","DOIUrl":"10.1016/j.intimp.2026.116340","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder characterized by multisystem complications, among which abnormal bone metabolism constitutes a prominent clinical challenge. Periostin (POSTN) plays a pivotal role in regulating the survival, adhesion, differentiation, and proliferation of osteoblasts and mesenchymal stem cells, thereby maintaining bone biomechanical integrity, mediating mechanotransduction, and facilitating fracture healing. The present study aimed to investigate POSTN expression in the T2DM microenvironment and elucidate its functional role and underlying mechanisms in the osteogenic differentiation of bone marrow mesenchymal stem cells derived from T2DM rats (T2DM-BMSCs). BMSCs were isolated from normal Sprague-Dawley (SD) rats and T2DM-SD rats, respectively. The POSTN expression was quantified using RT-qPCR and ELISA, while cell viability was evaluated via live/dead cell staining. Cellular senescence was assessed through DCFH-DA fluorescent probe staining for ROS accumulation and β-galactosidase staining. Autophagic capacity was determined using MDC fluorescent probes combined with WB analysis. The osteogenic differentiation potential was evaluated by ALP staining, alizarin red S staining, as well as RT-qPCR and WB analysis of osteogenic marker genes/proteins. Compared with normal BMSCs, T2DM-BMSCs exhibited significantly downregulated POSTN expression levels. Lentiviral-mediated POSTN knockdown via r-Postn shRNA resulted in reduced cell viability, elevated intracellular ROS production, accelerated cellular senescence, and impaired autophagic activity and osteogenic differentiation potential in both T2DM-BMSCs and BMSCs. Conversely, exogenous POSTN supplementation enhanced cell viability, mitigated ROS accumulation, alleviated cellular senescence, and ameliorated autophagic flux and osteogenic capacity in these cells. In conclusion, POSTN modulates the osteogenic differentiation of T2DM-BMSCs and normal BMSCs through the regulation of autophagic processes and cellular senescence, highlighting its potential as a therapeutic target for ameliorating bone metabolism disorders in T2DM.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116340"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193108","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}

{"title":"CSF hCG in the crossroads of neurotoxicity and disease: Lessons from germ cell tumor","authors":"Atoosa Etezadi ,&nbsp;Pooyan Alizadeh ,&nbsp;Nadia Talati Reveshti ,&nbsp;Armin Jahangiri Babadi ,&nbsp;Pedram Ghanavati","doi":"10.1016/j.intimp.2026.116321","DOIUrl":"10.1016/j.intimp.2026.116321","url":null,"abstract":"<div><h3>Background</h3><div>Human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) has emerged as a critical biomarker in the diagnosis, monitoring, and understanding of intracranial germ cell tumors (iGCTs). Beyond its canonical role in reproduction, CSF hCG dynamics may reflect intricate tumor biology, neuroimmune interactions, and paracrine signaling within the central nervous system.</div></div><div><h3>Objective</h3><div>This review critically examines the conceptual framework and clinical implications of CSF hCG as a defining biomarker axis in iGCTs, with a focus on its pathophysiological significance, dynamic regulation, and potential as a prognostic and therapeutic guide.</div></div><div><h3>Result</h3><div>CSF hCG levels are influenced by tumor subtype, burden, blood-brain barrier permeability, and local neuroinflammatory milieu. Dysregulated CSF hCG correlates with tumor activity, microenvironmental alterations, and neural tissue vulnerability, providing insight into both disease progression and potential neurotoxic sequelae. Mechanistic studies suggest that hCG in the CSF may modulate microglial activation, oxidative stress, neurotransmitter signaling, and blood-brain barrier integrity. While the causal links between hCG dynamics and neurological dysfunction remain to be fully elucidated, these patterns offer a unique window into tumor-host interactions within the CNS and highlight hCG as a potential axis for targeted monitoring and intervention.</div></div><div><h3>Conclusion</h3><div>CSF hCG represents more than a diagnostic marker; it embodies a dynamic biomarker axis integrating tumor biology, neurophysiological signaling, and clinical prognosis in iGCTs. Understanding its regulation and mechanistic roles could inform precision monitoring, risk stratification, and therapeutic strategies, bridging biomarker discovery with translational neuro-oncology.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116321"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193109","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}

{"title":"The human and murine immune systems: regulated by dichotomous molecules","authors":"Rafael Cardoso Maciel Costa Silva","doi":"10.1016/j.intimp.2026.116329","DOIUrl":"10.1016/j.intimp.2026.116329","url":null,"abstract":"<div><div>In this review, the important and dichotomous role of several receptors, inflammatory mediators and cells in the fine-tuning of immune responses in humans and mice is discussed. The underappreciated dichotomy of at least some molecules of the immune system, like PD-1, Gasdermin D and several cytokines, leads to unpredictable outcomes, especially when these molecules are targeted or manipulated for the treatment of distinct diseases. In this sense, this manuscript aims to highlight that, under particular situations, macromolecules involved in proinflammatory responses might lead to anti-inflammatory effects and vice versa. Understanding the mechanisms involved in this dichotomy might lead to specific therapies under certain conditions and/or important new molecular targets for the treatment of many diseases, minimizing collateral effects. In conclusion, this manuscript underscores how the immune system is controlled by the fine balance between the dichotomous effects of single molecules, depending on the circumstances.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"174 ","pages":"Article 116329"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192729","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}