International immunopharmacology最新文献

{"title":"Leveraging readily available clinical data with machine learning to predict first-line immunotherapy outcomes in non-small cell lung cancer","authors":"Fang Liu ,&nbsp;Rong Huang ,&nbsp;Qin Wang ,&nbsp;Ruitao Wang ,&nbsp;Jia Lu ,&nbsp;Yanying Zhang ,&nbsp;Xuejiao Ma ,&nbsp;Xiaoyu Liu ,&nbsp;Xudong Kong ,&nbsp;Pengmei Li ,&nbsp;Liqun Jia ,&nbsp;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}

{"title":"Hepatic ischemia-reperfusion and mitochondrial quality control: potential therapeutic targets","authors":"Junqi Wang ,&nbsp;Wenkai Fu ,&nbsp;Nan Lu ,&nbsp;Zhijiang Guo ,&nbsp;Ong Sang Bing ,&nbsp;Hongshuo Shi ,&nbsp;Hao Zhou ,&nbsp;Xing Chang ,&nbsp;Miao Meng","doi":"10.1016/j.intimp.2025.115267","DOIUrl":"10.1016/j.intimp.2025.115267","url":null,"abstract":"<div><h3>Background</h3><div>Hepatic ischemia-reperfusion injury (HIRI) represents a significant challenge in liver surgical procedures. This complex pathology arises from the interplay of inflammation, oxidative damage, and regulated cell death cascades. Compromised mitochondrial function critically contributes to HIRI progression. Consequently, maintaining cellular equilibrium necessitates effective mitochondrial quality control (MQC), a fundamental axis encompassing mitochondrial autophagy, dynamic remodeling, biogenesis, and the mitochondrial unfolded protein response (UPRmt).</div></div><div><h3>Key Mechanisms</h3><div>Mitophagy: Selectively removes damaged mitochondria via PINK1/Parkin (ubiquitin-dependent) and BNIP3/FUNDC1 (ubiquitin-independent) pathways. Impaired mitophagy during ischemia-reperfusion exacerbates mitochondrial damage, while enhancing it (e.g., via PEG35, Sirtuin activators) mitigates injury.</div><div>Mitochondrial Dynamics: The stability of the mitochondrial network is critically dependent on the equilibrium between fusion, regulated by Mfn1, Mfn2, and Opa1, and fission, mediated by Drp1. HIRI disrupts this equilibrium, promoting fragmentation and apoptosis. Pharmacological agents (e.g., DEX, exogenous irisin) restore dynamics by modulating Drp1 and fusion proteins.</div><div>Biogenesis: The PGC-1α/NRF-1/TFAM axis drives mitochondrial renewal. HIRI suppresses biogenesis, but interventions (e.g., ADSC-exo, genipin) enhance ATP production and mitochondrial DNA replication.</div></div><div><h3>Therapeutic Interventions</h3><div>Pharmacological strategies targeting MQC components demonstrate efficacy:</div><div>Mitophagy: PEG35 enhances ALDH2-mediated LC3 conversion; quercetin regulates SIRT1/TMBIM6.</div><div>Dynamics: COX-2 inhibitors and SIRT3 deacetylate Opa1 to promote fusion.</div><div>Biogenesis: Irisin and NRF2 activators upregulate PGC-1α/TFAM, restoring mitochondrial mass.</div></div><div><h3>Conclusion</h3><div>MQC mechanisms are pivotal in HIRI pathogenesis. Targeting mitophagy, dynamics, and biogenesis offers promising therapeutic avenues to attenuate inflammation, oxidative stress, and cell death. Translational research on MQC modulators (e.g., PEG35, Sirt1 activators) may yield novel treatments.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115267"},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694721","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":"Comment on: Oleoylethanolamide exerts neuroprotection following ischemic stroke through microglial PPARα signal","authors":"Keping Jiao ,&nbsp;Huiqin Zhang ,&nbsp;Yanyan Wang ,&nbsp;Jian Liu","doi":"10.1016/j.intimp.2025.115228","DOIUrl":"10.1016/j.intimp.2025.115228","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115228"},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694722","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":"Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis eukaryotic-prokaryotic dual expressing OVA enhances antitumor efficacy by both direct and cross-presentation","authors":"Tingting Zhang ,&nbsp;Shuai Huang ,&nbsp;Peng Liu ,&nbsp;Xiaoqiu Su ,&nbsp;Jiahe Zou ,&nbsp;Yulin Wu ,&nbsp;Yijie Li ,&nbsp;Yuekang Xu ,&nbsp;Jinyao Li","doi":"10.1016/j.intimp.2025.115263","DOIUrl":"10.1016/j.intimp.2025.115263","url":null,"abstract":"<div><div>Probiotic <em>Lactococcus lactis</em> (<em>L.L</em>) can act as an antigen delivery carrier to cross-present (XPT) exogenous antigens in dendritic cells (DCs). To optimize antigen XPT in a DC-based vaccine for improved antitumor efficacy, we produced recombinant <em>L.L</em> strains expressing the model antigen OVA <em>via</em> distinct methods: prokaryotic expression alone, eukaryotic expression alone, or dual prokaryotic-eukaryotic expression (designated <em>pOVA-L.L</em>, <em>eOVA-L.L</em>, and <em>dOVA-L.L</em>, respectively). These strains were used to deliver antigens into DCs. Although all three recombinant OVA-<em>L.L</em> strains significantly enhanced DCs' ability to promote OT-I cell proliferation (with <em>dOVA-L.L</em>-treated DCs (<em>dOVA-L.L</em>-DCs) showing the strongest effect), only <em>dOVA-L.L</em>-DCs demonstrated significantly more potent antitumor efficacy in the B16-OVA tumor mouse model, consistent with the <em>in vitro</em> data. Further investigation into the mechanisms underlying the enhanced antigen XPT and anti-tumor efficacy of <em>dOVA-L.L</em>-DCs revealed that <em>pOVA-L.L</em> and <em>dOVA-L.L</em> resided both inside and outside lysosomes, whereas <em>eOVA-L.L</em> was located exclusively outside lysosomes. Consequently, <em>dOVA-L.L</em>-DCs could XPT higher amounts of MHC I-OVA peptide complex on their surface. Furthermore, these DCs could also directly present lysosome-derived OVA peptide-MHC II complexes to stimulate antigen-specific CD4⁺ T cell responses <em>in vivo</em>. Collectively, these mechanisms induced more persistent cellular immune responses than either of the other two recombinant <em>L.L</em>-DCs. In conclusion, we developed an enhanced antigen delivery system using probiotic food-grade bacteria. This system promotes the prolonged expression of exogenous antigens and significantly enhances the XPT capacity of DC vaccines for tumor immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115263"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685535","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":"Knockdown of Nr4a3 mitigates acute pancreatitis-induced injury by modulating Btg2 to reduce oxidative stress, mitochondrial damage, and apoptosis","authors":"Zhongcheng Zhu ,&nbsp;Xiaolin Dou ,&nbsp;Qizhen Chen ,&nbsp;Yebin Lu","doi":"10.1016/j.intimp.2025.115269","DOIUrl":"10.1016/j.intimp.2025.115269","url":null,"abstract":"<div><div>Acute pancreatitis (AP) has a high mortality, involving oxidative stress and mitochondrial damage. Nuclear receptor subfamily 4 group A member 3 (Nr4a3) and BTG anti-proliferation factor 2 (Btg2) have a close connection with mitochondrial damage. Here, we found that Nr4a3 expression was upregulated in pancreatic tissues of AP mice induced by cerulein. To elucidate Nr4a3's role, we injected adeno-associated virus 9 (AAV9) carrying Nr4a3-targeting short hairpin RNA into the pancreatic duct. This intervention reduced pancreatic edema, inflammatory infiltration, and acinar cell necrosis by suppressing pancreatic enzyme activation. Moreover, Nr4a3 knockdown improved mitochondrial function in pancreatic acinar cells, evidenced by increased mitochondrial membrane potential, enhanced ATP production, and decreased superoxide levels. It also inhibited cell apoptosis by suppressing the activation of the caspase pathway. In vitro, Nr4a3 knockdown in CCK-treated pancreatic acinar cells decreased oxidative stress, mitigated mitochondrial damage, and suppressed apoptosis, while Nr4a3 overexpression exacerbated cell injury. Further investigation identified Btg2 as a downstream target of Nr4a3. Btg2 expression was elevated in pancreatic acinar cells of AP mice, and siRNA-mediated Btg2 knockdown alleviated CCK-induced cell injury. Mechanistically, Nr4a3 promoted Btg2 transcription, thereby promoting mitochondrial damage in pancreatic acinar cells and leading to cell apoptosis. Btg2 overexpression reversed the protective effects of Nr4a3 knockdown. Overall, our findings demonstrate that downregulation of Nr4a3 exerts anti-AP effects by regulating Btg2, providing potential therapeutic targets for AP.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115269"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685536","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":"Enzymatic synthesis and mechanistic insights into the hepatoprotective effects of α-monoglucosyl rutin against cyclophosphamide-induced liver injury: a multi-omics approach","authors":"Jing Tian ,&nbsp;Yanfeng Zhao ,&nbsp;Fanghang Li ,&nbsp;Yezhu Xu ,&nbsp;Wenting Yi ,&nbsp;Su Jiang ,&nbsp;Yunping Tang ,&nbsp;Yun Lu","doi":"10.1016/j.intimp.2025.115265","DOIUrl":"10.1016/j.intimp.2025.115265","url":null,"abstract":"<div><div>Rutin has attracted widespread attention due to its multiple pharmacological activities, but inherent defects such as poor water solubility and low bioavailability have greatly limited its clinical applications. Therefore, this study employed cyclodextrin glucanotransferase (CGTase) to catalyze the glycosylation modification of rutin, preparing rutin derivatives with improved water solubility. After optimizing the conditions, we isolated and purified 98.33 % of high-purity α-monoglucosyl rutin (α-GR), and its structure was also characterized. Subsequently, the cyclophosphamide (CTX)-induced murine liver injury model was used for activity evaluation. Our results showed that α-GR could significantly reduce liver function indicators (AST, ALT, and TBA), regulate antioxidant enzyme activities and inflammatory factor levels, and effectively attenuate CTX-induced liver injury. Furthermore, integrated metabolomics, transcriptomics, and RT-PCR analyses indicated that α-GR primarily exerts its hepatoprotective effects by intervening in key metabolites and gene expressions in CTX metabolic processes, related inflammatory responses, and oxidative stress pathways. Our results show that α-GR can effectively repair liver damage caused by CTX, thus laying the foundation for its use as a dietary supplement or therapeutic adjuvant.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115265"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694724","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":"Unveiling the potential therapeutic role of nifuroxazide and liraglutide combination in mitigating LPS-induced acute lung injury through modulation of AT1R/JAK-2/STAT-3 by ACE2/ Ang1‐7/MasR signaling in male albino rats: in vivo and in silico study","authors":"Amira Karam Khalifa ,&nbsp;Walla'’a A. Osman ,&nbsp;Ahmed Naeem Eesa ,&nbsp;Nagwa Mahmoud Ramadan ,&nbsp;Abeer Abdelkader ,&nbsp;Sara Sayed Kadry Abdallah ,&nbsp;Basma Emad Aboulhoda ,&nbsp;Fatma Al-Zahraa Nabil Al-Shahed ,&nbsp;Mansour A. Alghamdi ,&nbsp;Ahmed A. Elrashedy ,&nbsp;Mohamed Mahmoud Abdelrahim Elshaer ,&nbsp;Sameh Saber ,&nbsp;Alaa Karam Mahmoud ,&nbsp;Taha Ashraf ,&nbsp;Lamiaa Mohammed Matter","doi":"10.1016/j.intimp.2025.115261","DOIUrl":"10.1016/j.intimp.2025.115261","url":null,"abstract":"<div><div>The current study investigated the possible therapeutic role of a combination of liraglutide and nifuroxazide in ameliorating the JAK2/STAT3/NFĸB signaling pathway by augmenting the counter-regulatory ACE2/Ang1-7/MAS receptor axis of the renin angiotensin system (RAS). This therapeutic potential was further verified through molecular dynamic simulation studies. Seventy-five male Wistar albino rats were randomly allocated into 5 groups. The groups included normal control, LPS-induced ALI, ALI + NIF treated group, ALI + LIR-treated group, and ALI + LIR + NIF-treated group.The study revealed the promising therapeutic role of the liraglutide and nifuroxazide combination in significantly improving 7-day survival rates, ameliorating metabolic acidosis, and dampening the inflammatory response (IL-6, TNFα, iNOS, MPO, IL-1β) in bronchoalveolar lavage fluid (BALF). This was supported by the effective alleviation of pulmonary leakage, as evidenced by a remarkable decrease in wet lung weight/body weight ratio and wet/dry lung ratio. Additionally, the combination restored the redox balance by enhancing levels of SOD, catalase, and GSH. The combination regimen also improved the inflammatory score in histopathological examination, increased Nrf2 expression, and reduced iNOS immunoreactivity. These effects were attributed to the downregulation of total and phosphorylated protein expression of JAK2/STAT3/NFβB, and the upregulation of mRNA expression of ACE2 receptor, MAS receptors, and pulmonary lung surfactant B. Our study, which combined molecular dynamic simulation and experimental validation, provides a comprehensive perspective on managing septic acute lung injury, positioning the liraglutide and nifuroxazide combination regimen as a promising candidate for the management of septic acute lung injury (S-ALI).</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115261"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685539","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":"Inhibition of Skp2 enhances anti-tumor immunity of macrophages by regulating CD47 in gastric cancer","authors":"Kaizhao Hu ,&nbsp;Lidan Zhao ,&nbsp;Peipei Miao ,&nbsp;Wenhui Qiu ,&nbsp;Lu Ai ,&nbsp;Xi Chen ,&nbsp;Sai-Qi Wang ,&nbsp;Xiaobing Chen ,&nbsp;Xiao-Jing Shi","doi":"10.1016/j.intimp.2025.115262","DOIUrl":"10.1016/j.intimp.2025.115262","url":null,"abstract":"<div><div>S-phase kinase-associated protein 2 (Skp2), a member of the ubiquitin E3 ligase F-box family, has been confirmed to control the tumorigenesis and progression of varieties of tumors, and is a potential pharmacological target for anticancer therapy. Recent research reveal that Skp2 affects tumor immune microenvironment through regulating immune checkpoints. However, the effect of Skp2 on the tumor microenvironment (TME) and its underlying regulatory mechanism in gastric cancer is still unclear. This study was aim to investigate the role of Skp2 in gastric cancer immunotherapy. Through database and experimental analysis, it was found that inhibition of Skp2 could reduce the expression of tumor immune checkpoint CD47. Co-culture experiments <em>in vitro</em> showed that inhibition of Skp2 could enhance the phagocytosis of macrophages on gastric cancer cells. Further studies showed that Skp2 affected the expression of the lysosomal protein RAGA and regulated the degradation of CD47 lysosomes. Subsequently, a gastric cancer SNU601 xenograft model also showed that inhibition of Skp2 downregulated CD47 levels <em>in vivo</em>. Small inhibitor of Skp2 combined with 5-FU chemotherapy could synergistically inhibit tumor growth, which affected the changes of immune microenvironment and regulated the infiltration of macrophages. To sum up, this study confirmed that Skp2 as an important regulator of phagocytosis and provided a new theoretical basis for improving anti-tumor immune efficacy and related drug development.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115262"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694726","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":"Nature's answer to Ferroptosis: how bioactive compounds rewire oxidative stress circuits in cerebral ischemia","authors":"Yaqiao Yi ,&nbsp;Xuan Zhu ,&nbsp;Pu Jia ,&nbsp;Weicai Cai ,&nbsp;Lin Liu","doi":"10.1016/j.intimp.2025.115250","DOIUrl":"10.1016/j.intimp.2025.115250","url":null,"abstract":"<div><div>Ischemic stroke is a cerebrovascular disease caused by the interruption of local blood flow in the brain. The mechanism of cerebral ischemia-reperfusion injury (CIRI) is complex and involves multiple pathological processes and signaling pathways. Ferroptosis, an iron-dependent regulated cell death form caused by excessive lipid peroxidation, is associated with the pathological occurrence and therapeutic response of various types of neurodegenerative diseases. Increased iron accumulation, free radical production, fatty acid supply, and lipid peroxidation are key factors in inducing ferroptosis. After acute ischemic stroke, the body experiences an over-accumulation of iron, lipid peroxidation, and reactive oxygen species in the cytoplasm by affecting neural system iron metabolism, lipid metabolism, and amino acid metabolism. This leads to the induction of ferroptosis. This article reviews the three metabolic pathways (iron metabolism pathway, amino acid metabolism pathway, lipid metabolism pathway, (seleno)thiol metabolism pathway, citric acid pathway, etc.) and multiple related regulatory signaling pathways (Nrf2 pathway; (hemi)cysteine/GSH/GPX4 pathway, NAD(<em>P</em>)H/FSP1/CoQ10 pathway; GCH1/BH4/DHFR signaling pathway; etc.) involved in ferroptosis occurrence in neural cells following acute ischemic stroke. It also highlights the changes in several key regulatory molecules, such as hypoxia-inducible factor-1α (HIF-1α), BTB and CNC homology 1 (BACH1), tumor suppressor gene p53, nuclear receptor coactivator 4 (NCOA4), and activating transcription factor 3 (ATF3), and the downstream mechanisms regulated by these molecules. Through an analysis of the potential mechanisms of ferroptosis occurrence and development in ischemic stroke, this article aims to provide reference for effective treatment of ischemic stroke and improvement of patient prognosis. Meanwhile, this review proposes a synergistic model of the “ferroptosis–oxidative stress–neuroinflammation” triad in ischemic stroke for the first time, providing a theoretical foundation for the development of neuroprotective agents based on natural compounds.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115250"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694725","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":"Myricetin alleviates DNCB-induced atopic dermatitis by modulating macrophage M1/M2 polarization","authors":"XinJia Zhang ,&nbsp;Jing Li ,&nbsp;YanJiao Liu,&nbsp;RuiJu Ma,&nbsp;ChuYao Li,&nbsp;ZhiChang Xu,&nbsp;RuiRui Wang,&nbsp;LiJuan Zhang,&nbsp;Yi Zhang","doi":"10.1016/j.intimp.2025.115212","DOIUrl":"10.1016/j.intimp.2025.115212","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Atopic dermatitis (AD), a chronic and relapsing inflammatory skin disease, is characterized by recurrent eczema, itch, and pain. Conventional treatments, such as topical corticosteroids, are associated with various adverse effects. Previous studies have shown that Myricetin (Myr) effectively treats AD and inflammation induced by DNFB and MC903. However, the mechanism of Myricetin remains poorly understood. This study aims to investigate the therapeutic effects of Myricetin on DNCB-induced AD and to elucidate the underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An AD model was established with DNCB to evaluate the effectiveness of Myricetin by daily intraperitoneal injection at dosages of 2, 4, and 6 mg/kg. The Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of inflammatory cytokines/chemokines in ear tissues, Masson's staining was used to assess collagen loss, Immunofluorescence was used to identify macrophage infiltration in skin tissue, and Western blot was employed to detect the expression of proteins associated with M1 and M2 macrophage polarization. To investigate the underlying mechanism in vitro, RAW264.7 cells were employed for macrophage polarization analysis. M1 macrophages phenotype was induced with LPS + IFN-γ, whereas M2 macrophages phenotype was induced by IL-4. The Griess assay method was used to detect the content of NO, and the Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of IL-6, TNF-α, IL-1β, and IL-10 in M1 macrophage culture medium. Western blot was employed to detect the proteins expression of JAK1, JAK2, STAT1, IκB-α, P65, and iNOS in M1 macrophages. In M2 macrophages, Western blot was employed to detect the proteins expression of JAK1, JAK2, STAT1, STAT6, and Arg-1.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Myricetin ameliorated skin lesions of DNCB-induced AD mice by reduced levels of pro-inflammatory chemokines/cytokines (IL-18, CXCL-9, CXCL-10), attenuated collagen loss in ear lesions, increased levels of the anti-inflammatory factors TGF-β1 and IL-10, increased the number of F4/80/CD206 positive cells and decreased the infiltration of F4/80/CD86 positive cells, suppressed iNOS protein expression and reduced the phosphorylation of STAT1, IκB-α, and P65, while enhancing Arg-1 expression and STAT6 phosphorylation. In vitro studies have demonstrated that Myricetin effectively suppressed the content of inflammatory factors such as IL-6, TNF-α, NO, and IL-1β, while elevating IL-10 concentration, reduced the proteins expression of p-JAK1, p-STAT1 (Tyr701), p-IκB-α, p-P65, and iNOS, in M1 macrophages. In M2 macrophages, Myricetin increased the expression of Arg-1 and phosphorylation of STAT6 protein expression, lowered the expression of phosphorylation of JAK1 protein expression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our findings demonstrate that Myricetin significantly ameliorates skin lesions of DNCB-induced AD mice and reduces inflammat","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"163 ","pages":"Article 115212"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685540","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}