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4-Methylesculetin attenuates inflammatory pain via inhibition of Sp1-TRPV1 and inflammation related signaling pathways
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-06 DOI: 10.1016/j.intimp.2025.114379
Weixin Zhao , Mengyu Chen , Xialin Yu , Huayu Zhong , Shikang Hao , Shuangyu Liu , Ziyu Tian , Lilong Dong , Shijie Dai , Haiyan Liu , Han Hao
{"title":"4-Methylesculetin attenuates inflammatory pain via inhibition of Sp1-TRPV1 and inflammation related signaling pathways","authors":"Weixin Zhao ,&nbsp;Mengyu Chen ,&nbsp;Xialin Yu ,&nbsp;Huayu Zhong ,&nbsp;Shikang Hao ,&nbsp;Shuangyu Liu ,&nbsp;Ziyu Tian ,&nbsp;Lilong Dong ,&nbsp;Shijie Dai ,&nbsp;Haiyan Liu ,&nbsp;Han Hao","doi":"10.1016/j.intimp.2025.114379","DOIUrl":"10.1016/j.intimp.2025.114379","url":null,"abstract":"<div><h3>Background</h3><div>Discovering lead compounds with anti-inflammatory and analgesic activities from natural products with minimal toxic side effects has been a long-term goal for researchers. 4-Methylesculetin (4-ME), a natural coumarin derivative, has been reported to have anti-inflammatory and antioxidant properties, but its analgesic effect has not yet been studied. This research investigates the analgesic effect and underlying mechanism of 4-ME in peripheral inflammatory pain.</div></div><div><h3>Methods</h3><div>Acute or chronic inflammatory pain model was established by injecting formalin or Complete Freund's Adjuvant (CFA) into the right hindpaw of rat, respectively. The mechanical and thermal thresholds were detected by using Von Frey and thermal radiation instrument. Patch-clamp recording was performed to study the electrophysiological properties of ion channel. RT-qPCR, western blot, and immunofluorescence were used to analyze mRNA and protein expressions of relevant signaling pathway molecules.</div></div><div><h3>Results</h3><div>Intraperitoneal injection of 4-ME could significantly alleviate mechanical and thermal hyperalgesia induced by CFA injection, as well as spontaneous pain induced by formalin injection. In the CFA-induced chronic pain model, 4-ME reduced the levels of IL-6, TNF-α, IL-1β, and inhibited ERK, NF-κB, NLRP3 pathways in dorsal root ganglia (DRG). It downregulated abnormally high expression of TRPV1 caused by CFA injection in DRG, without altering the electrophysiological properties of TRPV1 channel. Further mechanistic studies demonstrated that 4-ME regulated the expression of TRPV1 by inhibiting the transcription factor Sp1. Compared to other coumarin derivatives, 4-ME exhibited a better analgesic effect at low dosage.</div></div><div><h3>Conclusion</h3><div>Our study reveals for the first time that 4-ME could alleviate peripheral inflammatory pain by inhibiting Sp1-TRPV1 pathway, suggests 4-ME as a potential analgesic, and provides a theoretical basis for 4-ME translation into clinical application.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114379"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548203","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}
引用次数: 0
Research progress on pharmacokinetics, anti-inflammatory and immunomodulatory effects of kaempferol
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-06 DOI: 10.1016/j.intimp.2025.114387
Suiran Li , Siwei Wang , Lei Zhang , Yuxiu Ka , Meijiao Zhou , Yiwen Wang , Zhuo Tang , Jiamin Zhang , Wen Wang , Wei Liu
{"title":"Research progress on pharmacokinetics, anti-inflammatory and immunomodulatory effects of kaempferol","authors":"Suiran Li ,&nbsp;Siwei Wang ,&nbsp;Lei Zhang ,&nbsp;Yuxiu Ka ,&nbsp;Meijiao Zhou ,&nbsp;Yiwen Wang ,&nbsp;Zhuo Tang ,&nbsp;Jiamin Zhang ,&nbsp;Wen Wang ,&nbsp;Wei Liu","doi":"10.1016/j.intimp.2025.114387","DOIUrl":"10.1016/j.intimp.2025.114387","url":null,"abstract":"<div><div>Chronic inflammation (an abnormal state) and autoimmune disease (AD) can both cause multiple organ damage. AD is a heterogeneous group of diseases due to immune dysfunction. Chronic inflammation is closely related to AD and is an important part of AD. With the increasing prevalence of AD, researchers are constantly exploring new drugs with small side effects, considerable curative effects, and lower costs. Kaempferol, a flavonoid, possesses a range of biological functions, including antioxidant, anti-inflammatory, anti-neoplastic, and immunomodulatory capabilities. This compound is prevalent in a variety of plant sources, such as vegetables, fruits, and medicinal herbs traditionally used in Chinese medicine. A plethora of empirical evidence from animal-based research supports the assertion that this particular substance exhibits both anti-inflammatory and immunomodulatory effects, with the curative effect being significant and application prospects. This article mainly summarizes and discusses the pharmacokinetics, drug delivery system, and the mechanism of kaempferol on immune cells, cytokines, signaling pathways, and other aspects. This paper summarizes the existing kaempferol drug delivery system, analyzes the possibility and limitations of kaempferol as a new anti-inflammatory and immunomodulatory drug, and discusses how to apply it in clinical practice. Therefore, kaempferol can more effectively exert its anti-inflammatory and immune-modulating effects, thereby demonstrating therapeutic potential in clinical settings, while reducing patient burden.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114387"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562288","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}
引用次数: 0
Anethole trithione mitigates LPS/D-Gal-induced acute liver injury by suppressing ROS production and NF-κB activity
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-06 DOI: 10.1016/j.intimp.2025.114371
Zhen He , Xiangyun Tan , Ming Yuan , Liang Chen , Yan Meng , Qi Wang , Junjie Hu , Zhenpeng Qiu , Yuan Yang
{"title":"Anethole trithione mitigates LPS/D-Gal-induced acute liver injury by suppressing ROS production and NF-κB activity","authors":"Zhen He ,&nbsp;Xiangyun Tan ,&nbsp;Ming Yuan ,&nbsp;Liang Chen ,&nbsp;Yan Meng ,&nbsp;Qi Wang ,&nbsp;Junjie Hu ,&nbsp;Zhenpeng Qiu ,&nbsp;Yuan Yang","doi":"10.1016/j.intimp.2025.114371","DOIUrl":"10.1016/j.intimp.2025.114371","url":null,"abstract":"<div><div>Acute liver injury (ALI) is a prevalent form of hepatic disease associated with significant morbidity and mortality due to medical treatments, exposure to toxins or viral infections. Anethole trithione (ATT) is a heterocyclic sulfur compound recognized for its chemoprotective properties against cancer and drug-induced toxicity. This study aimed to evaluate the effectiveness of ATT in the treatment of ALI. The therapeutic effects of ATT on hepatic injury were evaluated in vivo by inducing ALI in mice through the administration of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Additionally, HepG2 and Huh7 cells exposed to LPS were utilized to investigate the underlying mechanisms in vitro. The results indicated that ATT significantly reduced the production of reactive oxygen species (ROS), mitigated oxidative stress-related biochemical markers, and inhibited hepatocyte apoptosis in vivo, resulting in marked improvement in ALI in the murine model. Mechanistic studies conducted both in vivo and in vitro demonstrated that ATT alleviates LPS/D-Gal-induced ALI by inhibiting ROS production and the activity of nuclear factor-kappa B (NF-κB). Collectively, these findings underscore the potential therapeutic benefits of ATT in the management of ALI.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114371"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548204","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}
引用次数: 0
Administration of hypoxic pretreated adipose-derived mesenchymal stem cell exosomes promotes spinal cord repair after injury via delivery of circ-Astn1 and activation of autophagy
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114324
Minghao Shao , Mingming Jin , Lv Feizhou , Xiaosheng Ma , Zhu Wei
{"title":"Administration of hypoxic pretreated adipose-derived mesenchymal stem cell exosomes promotes spinal cord repair after injury via delivery of circ-Astn1 and activation of autophagy","authors":"Minghao Shao ,&nbsp;Mingming Jin ,&nbsp;Lv Feizhou ,&nbsp;Xiaosheng Ma ,&nbsp;Zhu Wei","doi":"10.1016/j.intimp.2025.114324","DOIUrl":"10.1016/j.intimp.2025.114324","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to investigate the role and mechanism of exosomes isolated from adipose-derived mesenchymal stem cells (ADSCs) on spinal cord repair.</div></div><div><h3>Methods</h3><div>High-throughput sequencing was used to investigate abnormal expression of circular RNA (circRNA) in ADSC exosomes pretreated under hypoxic conditions (HExos) and ADSCs exosomes under normal conditions (Exos). The abnormal expression of mRNA in spinal cord tissues was also analyzed using high-throughput sequencing. Bioinformatics and luciferase reporter analyses were used to clarify the relationship among circRNA, micro RNA (miRNA), and mRNA. BV2 cells were used to analyze apoptosis levels and inflammatory cytokine expression under oxygen-glucose deprivation (OGD) conditions by using immunofluorescence and enzyme-linked immunosorbent assay (ELISAs). An SCI mouse model was also constructed and the therapeutic effect of Exos was detected using immunohistochemistry and immunofluorescence.</div></div><div><h3>Results</h3><div>High-throughput sequencing results showed that circ-Astn1 played a role in HExo-mediated spinal cord repair after SCI. Downregulation of circ-Astn1 decreased the therapeutic effect of HExos. We also found that Atg7 played a role in HExo-mediated spinal cord repair after SCI. Luciferase reporter analysis confirmed that both miR-138-5p and Atg7 were downstream targets of circ-Astn1. Downregulation of Atg7 or overexpression of miR-138-5p reversed the protective effect of circ-Astn1 on BV2 cells after exposure to OGD conditions. In contrast, upregulation of circ-Astn1 increased the therapeutic effects of Exo-mediated spinal cord repair after SCI via autophagy activation.</div></div><div><h3>Conclusions</h3><div>Taken together, the results indicate that ADSC-Exos containing circ-Astn1 promoted spinal cord repair after SCI by targeting the miR-138-5p/Atg7 pathway, which mediated autophagy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114324"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548202","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}
引用次数: 0
Monocytes from patients with myelodysplastic syndrome inhibit natural killer cell-mediated antitumor function through the CD200/CD200R pathway
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114394
Yixuan Guo , Zhaoyun Liu , Mengyue Tian , Xiaohan Liu , Nianbin Li , Kai Ding , Hui Liu , Rong Fu
{"title":"Monocytes from patients with myelodysplastic syndrome inhibit natural killer cell-mediated antitumor function through the CD200/CD200R pathway","authors":"Yixuan Guo ,&nbsp;Zhaoyun Liu ,&nbsp;Mengyue Tian ,&nbsp;Xiaohan Liu ,&nbsp;Nianbin Li ,&nbsp;Kai Ding ,&nbsp;Hui Liu ,&nbsp;Rong Fu","doi":"10.1016/j.intimp.2025.114394","DOIUrl":"10.1016/j.intimp.2025.114394","url":null,"abstract":"<div><h3>Background</h3><div>Reports on the expression of CD200 in monocytes are scarce, and the role of monocytes in patients with myelodysplastic syndrome (MDS) remains unclear. Additionally, monocytes have been implicated in suppressing NK cell function. Therefore, this study aimed to explore the possible mechanism by which monocytes regulate NK cell function through CD200 in patients with MDS.</div></div><div><h3>Methods</h3><div>We collected samples from patients with MDS, those with acute myeloid leukemia, and healthy controls. We detected the expression of CD200 on the surface of monocytes and its receptor CD200R on the surface of NK cells using flow cytometry, explored the effect of the CD200/CD200R pathway on activating STAT3 and ERK of NK cells, and studied the effect of blocking CD200/CD200R pathway on NK cells.</div></div><div><h3>Results</h3><div>The expression of CD200 on the surface of monocytes and CD200R on the surface of NK cells in patients with MDS was higher than those in healthy controls. After adding CD200 monoclonal antibody to the co-culture system of monocytes and NK cells, the expression of activated receptors CD107a, CD226, and NKG2D on NK cells significantly increased. We then used siRNA to silence CD200R expression in NK-92 cells and found that the blockade of CD200R enhanced the phosphorylation levels of ERK and STAT3.</div></div><div><h3>Conclusions</h3><div>Our study found that elevated CD200 expression on monocytes in patients with MDS correlates with poor prognosis, suggesting CD200 as a potential prognostic marker. Blocking CD200 enhances NK cell activation and cytotoxicity, indicating that CD200 blockade therapy could enhance antitumor responses in patients with MDS.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114394"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548306","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}
引用次数: 0
The clathrin adaptor AP1-S1 is associated with immune infiltration and HLA loss, as a potential therapeutic target in lung adenocarcinoma
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114385
Yafei Liu , Feng Li , Bin Wu , Lan Huang , Yu Qi
{"title":"The clathrin adaptor AP1-S1 is associated with immune infiltration and HLA loss, as a potential therapeutic target in lung adenocarcinoma","authors":"Yafei Liu ,&nbsp;Feng Li ,&nbsp;Bin Wu ,&nbsp;Lan Huang ,&nbsp;Yu Qi","doi":"10.1016/j.intimp.2025.114385","DOIUrl":"10.1016/j.intimp.2025.114385","url":null,"abstract":"<div><div>The clathrin adaptor protein 1 (AP1) plays a pivotal role in the endocytosis of cell surface proteins and transportation between the golgi apparatus and lysosomes. Despite its critical functions, the implications of AP1 dysregulation in human cancers have yet to be elucidated. The structural analysis of AP1 subunits was conducted utilizing data from the Protein Data Bank (PDB), which is composed of four subunits: AP1-S1, AP1-B1, AP1-G1, and AP1-M1. Notably, the expression levels of AP1 subunits exhibit significant variability between tumor and normal tissues across different cancer types using data from the CPTAC, GEO, and TCGA databases. Kaplan-Meier (K-M) curve analysis has revealed that certain AP1 subunits are correlated with patient prognosis in various cancers. For instance, the AP1-S1 subunit is related to poor survival outcomes in head and neck squamous carcinoma, clear cell renal cell carcinoma, and lung adenocarcinoma. Furthermore, the aberrant expression of AP1-S1 demonstrated a negative correlation with immune cells infiltration, particularly in lung adenocarcinoma. Concurrently, a significant negative relationship between AP1-S1 and HLA molecules was observed, indicating a potential mechanism for AP1-induced HLA degradation. <em>In vitro</em> experiments demonstrated that the knockdown of AP1-S1 led to an upregulation of HLA-B protein expression and inhibited the viability, migration, and invasion capabilities of tumor cells in lung adenocarcinoma cell lines, specifically A549 and H1299. Immunohistochemical staining further revealed the abnormal expression of AP1-S1 in lung adenocarcinoma specimens. Through a comprehensive pan-cancer multi-omics analysis and experimental validation, this study explored the prognostic significance of four AP1 subunits. Additionally, it examined the regulatory relationship between AP1-S1 and HLA-B, which may play a role in immune escape. Additionally, the research identified AP1-S1 as a valuable biomarker and a potential target for treatment of lung adenocarcinoma.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114385"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548316","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}
引用次数: 0
The efficacy of ICIs rechallenge in advanced small cell lung cancer after progression from ICIs plus chemotherapy: A real-world study
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114372
Fen Liu , Guisen Yin , Ye Tao , Yong Pan
{"title":"The efficacy of ICIs rechallenge in advanced small cell lung cancer after progression from ICIs plus chemotherapy: A real-world study","authors":"Fen Liu ,&nbsp;Guisen Yin ,&nbsp;Ye Tao ,&nbsp;Yong Pan","doi":"10.1016/j.intimp.2025.114372","DOIUrl":"10.1016/j.intimp.2025.114372","url":null,"abstract":"<div><h3>Background</h3><div>Rechallenging immune checkpoint inhibitors(ICIs) after resistance to initial ICIs plus chemotherapy(chemo-ICIs) remains uncertain in advanced small cell lung cancer(SCLC).</div></div><div><h3>Method</h3><div>The study retrospectively enrolled advanced SCLC patients who received ICIs after developing resistance to chemo-ICIs during hospitalization at Hunan Cancer Hospital from January 2020 to November 2023. The clinical outcomes and prognosis factors for ICIs rechallenge were further analyzed.</div></div><div><h3>Results</h3><div>A total of 175 patients were included, of which 82(46.86 %) patients had primary resistance(PR) and 93(53.14 %) patients developed acquired resistance(AR). The progression-free survival(PFS), objective response rate (ORR), and disease control rate (DCR) of the total group were 3.3 months,16.57 %, and 53.71 %, respectively. The AR group exhibited significantly longer PFS compared to the PR group (4.5 months <em>vs.</em> 3.2 months, <em>p</em> = 0.012). In the PR group, a significantly longer PFS was found for ICIs rechallenge with interval treatment than without interval treatment(4.2 months <em>vs.</em> 3.1 months, <em>p</em> = 0.031). Within the AR group, the “new immunotherapy plus new chemotherapy” regimen showed a significantly longer PFS compared to the regimen of “maintain immunotherapy plus new chemotherapy” (8.3 months <em>vs.</em> 3.2 months, <em>p</em> = 0.014). The multivariate COX regression analyses demonstrated that both resistance pattern(<em>p</em> = 0.007) and treatment regimen(<em>p</em> = 0.039) independently served as risk factors for PFS in ICIs rechallenge.</div></div><div><h3>Conclusion</h3><div>Our study suggests that rechallenge of ICIs could be considered as a potential therapeutic strategy for advanced SCLC after progression from chemo-ICIs, particularly in patients with AR.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114372"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Severe asthma beyond bronchodilators: Emerging therapeutic approaches
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114360
Muhammad Qasim Barkat , Majid Manzoor , Chengyun Xu , Nadia Hussain , Ahmad Salawi , Hao Yang , Musaddique Hussain
{"title":"Severe asthma beyond bronchodilators: Emerging therapeutic approaches","authors":"Muhammad Qasim Barkat ,&nbsp;Majid Manzoor ,&nbsp;Chengyun Xu ,&nbsp;Nadia Hussain ,&nbsp;Ahmad Salawi ,&nbsp;Hao Yang ,&nbsp;Musaddique Hussain","doi":"10.1016/j.intimp.2025.114360","DOIUrl":"10.1016/j.intimp.2025.114360","url":null,"abstract":"<div><div>Asthma is characterized by reversible airway inflammation, obstruction, and structural remodeling, which lead to the eosinophils and lymphocytes accumulation at inflammation sites and the release of inflammatory cells, like mast cells and dendritic cells, from lungs' epithelial and smooth muscle cells that trigger the activation and release of cytokines and chemokines, attracting more cells and contributing to asthma development. Available pharmacological interventions, like bronchodilators and anti-inflammatory agents, are considered generally safe and effective to treat asthma, but many affected individuals with severe asthma still struggle with symptom control. This review highlights recent innovative therapies, such as chemoattractant receptor-homologous molecule expressed on Th2 cell (CRTH2) antagonists, S-nitrosoglutathione reductase (GSNOR) and phosphodiesterase (PDE) inhibitors, and other novel biological agents, which offer potential new strategies for managing severe asthma and may alter the disease's course.</div><div>Kew words.</div><div>Inflammation; CRTH2; GSNOR; PDE; Interleukins; Biological agents.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114360"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548307","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}
引用次数: 0
Activation of the hippocampal CA1 astrocyte Gq and Gi G protein-coupled receptors exerts a protective effect against attention deficit hyperactivity disorder
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.intimp.2025.114382
Yu-Dong Shan , Zhi-Fang Yu , Ge-Ge Lv , Yong-Lin Shan , Bao-Dong Li , Jian-Yong Zhao , Xiao-Ming Li , Wei-Juan Gao , Li-Min Zhang
{"title":"Activation of the hippocampal CA1 astrocyte Gq and Gi G protein-coupled receptors exerts a protective effect against attention deficit hyperactivity disorder","authors":"Yu-Dong Shan ,&nbsp;Zhi-Fang Yu ,&nbsp;Ge-Ge Lv ,&nbsp;Yong-Lin Shan ,&nbsp;Bao-Dong Li ,&nbsp;Jian-Yong Zhao ,&nbsp;Xiao-Ming Li ,&nbsp;Wei-Juan Gao ,&nbsp;Li-Min Zhang","doi":"10.1016/j.intimp.2025.114382","DOIUrl":"10.1016/j.intimp.2025.114382","url":null,"abstract":"<div><h3>Background</h3><div>Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms such as inattention, hyperactivity and impulsiveness, which significantly impact the healthy development of children. Our prior research demonstrated that exposure to S-Ketamine during pregnancy can lead to the development of ADHD, and existing studies have established a close association between astrocytes and the onset and progression of ADHD. The activation and inhibition of astrocytes are closely linked to neuropsychiatric dysfunction, and astrocytic NOD-like receptor protein 3 (NLRP3) has been reported to contribute to alterations in mental state and cognitive deficits. Thus, this study aims to investigate the role of astrocytes in ADHD by selectively modulating astrocyte function through Gq and Gi G protein-coupled receptors (GPCRs) and by specifically targeting the knockout of NLRP3.</div></div><div><h3>Methods</h3><div>Pregnant C57BL/6 J mice or mice with a specific deletion of NLRP3 in astrocytes were administered intraperitoneal injections of 15 mg/kg of S-ketamine for 5 consecutive days from gestational day 14 to 18 to establish an ADHD model. To modulate astrocyte activity in the hippocampal CA1 region, we administered astrocyte-specific Gq-Adeno-associated virus (AAV) or Gi-AAV into the CA1 and maintained treatment with CNO. At 21 days postnatally, we conducted open field test (OFT), novel object recognition (NOR), elevated plus maze (EPM) and fear conditioning (FC) in the offspring mice. Additionally, on postnatal day 21, we implanted electrodes in the CA1 region of the offspring mice for neurophysiological monitoring and investigated local field potentials (LFP) during NOR on postnatal day 27. Lastly, pathological assessments were conducted after euthanasia.</div></div><div><h3><strong>Results</strong></h3><div>Both the activation and inhibition of astrocytes in the hippocampal CA1 region improved impulsive-like behaviors and cognitive function in ADHD mice, reduced the power of theta (θ) oscillations during novel object exploration and decreased NLRP3-associated inflammatory factors, including cleaved caspase-1 and IL-18. Furthermore, compared to WT mice, astrocyte-specific NLRP3 conditional knockout mice demonstrated significantly reduced impulsive behavior and cognitive deficits, as well as a decrease in θ oscillation power and a reduction in NLRP3-associated inflammatory factors.</div></div><div><h3><strong>Conclusions</strong></h3><div>Our data provide compelling evidence that the activation of astrocytes alleviated impulsive-like behaviors and cognitive dysfunction, possibly by reducing NLRP3-associated pyroptosis following changes in calcium levels within the astrocytes. The activation of astrocytes can be a potential therapeutic target for ADHD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114382"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548315","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}
引用次数: 0
Corrigendum to "C-X-C-chemokine-receptor-type-4 as a potential target for diagnosis and treatment of acute radiation-induced esophagitis" [International Immunopharmacology 150 (2025) 114289].
IF 4.8 2区 医学
International immunopharmacology Pub Date : 2025-03-04 DOI: 10.1016/j.intimp.2025.114362
Jinli Pei, Shijie Wang, Kai Cheng, Shengnan Xu, Xinzhi Zhao, Kunlong Zhao, Yuxi Luo, Wanhu Li, Jinming Yu, Jie Liu
{"title":"Corrigendum to \"C-X-C-chemokine-receptor-type-4 as a potential target for diagnosis and treatment of acute radiation-induced esophagitis\" [International Immunopharmacology 150 (2025) 114289].","authors":"Jinli Pei, Shijie Wang, Kai Cheng, Shengnan Xu, Xinzhi Zhao, Kunlong Zhao, Yuxi Luo, Wanhu Li, Jinming Yu, Jie Liu","doi":"10.1016/j.intimp.2025.114362","DOIUrl":"https://doi.org/10.1016/j.intimp.2025.114362","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"114362"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566877","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}
引用次数: 0
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