Current molecular medicine最新文献

{"title":"Systemic Pharmacology & Molecular Docking: Probe Quince Seeds' Cough Suppressant Mechanism.","authors":"Yan Li, Zichen Yao, Yongwei Liu","doi":"10.2174/0115665240446700260422053741","DOIUrl":"https://doi.org/10.2174/0115665240446700260422053741","url":null,"abstract":"<p><strong>Introduction: </strong>Quince seeds (WBZ) are a traditional herbal remedy for cough, but their pharmacological mechanisms remain incompletely understood. This study aims to clarify the antitussive mechanism of WBZ using a systems pharmacology approach.</p><p><strong>Methods: </strong>Active compounds in WBZ were screened according to ADME criteria. Direct targets were predicted using a Weighted Ensemble Similarity (WES) model. Pathway enrichment analyses (GO and KEGG) were performed on the predicted targets. This was integrated with differential gene expression analysis from an asthma/COPD dataset (GSE148004). Key compound-target interactions were validated via molecular docking.</p><p><strong>Results: </strong>We identified 25 active compounds targeting 143 human proteins. Enrichment analysis highlighted key pathways, including serotonergic synapse, calcium signaling, and inflammatory mediator regulation of TRP channels. Molecular docking confirmed strong binding of core compounds (e.g., quercetin, oleanolic acid) to central targets such as HTR1A, HTR2A, and PRKCB.</p><p><strong>Discussion: </strong>Mechanistically, WBZ appears to exert antitussive effects through a dual Central-peripheral Mechanism. Centrally, components like quercetin may target presynaptic HTR1A to modulate the cough reflex. Peripherally, inhibition of HTR2A and PRKCB could alleviate bronchoconstriction, while ADCY5 modulation may reduce TRP channel sensitization via cAMP signaling. This multi-target synergy provides a plausible explanation for WBZ's traditional use in cough relief.</p><p><strong>Conclusion: </strong>This study comprehensively delineates the systemic mechanism of WBZ against cough, offering a theoretical foundation for its clinical application and further development. The integrative strategy combining systems pharmacology with molecular docking presents a useful paradigm for researching complex herbal medicines.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture Attenuates Lipopolysaccharide-Induced Acute Lung Injury via Enhanced Efferocytosis.","authors":"Jing Liu, Fang Liu, Guihua Lai, Mengjian Qu, Mengmeng Li, Jia Fu, Jun Zhou, Zhilu Sun","doi":"10.2174/0115665240451541260423114707","DOIUrl":"https://doi.org/10.2174/0115665240451541260423114707","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate whether efferocytosis, the phagocytic clearance of apoptotic cells, contributes to the therapeutic mechanism of EA in a lipopolysaccharide (LPS)-induced rat model of Acute Lung Injury (ALI).</p><p><strong>Methods: </strong>Three-month-old rats were randomly assigned to control, LPS, and LPS + EA groups (n = 8/group). Daily EA was administered at the bilateral ST36 (Zusanli) and LU5 (Chize) acupoints in the LPS + EA group. Lung tissue damage and cellular death were assessed using histological analysis and TUNEL staining. Serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 were quantified by ELISA. Key markers associated with apoptosis and efferocytosis were assessed by qRT-PCR and Western blotting.</p><p><strong>Results: </strong>Histopathological examination showed that EA alleviated LPS-induced lung tissue damage and attenuated inflammatory cell infiltration. Following EA intervention, serum levels of TNF-α, IL-1βand IL-6 were decreased, while the level of IL-10 was increased. Massive accumulation of dead cells was observed in the lung tissue of ALI rats; LPS exposure significantly downregulated the mRNA and protein expression levels of Axl, Mertk and Rac1, while upregulating the expression level of Gas6 in lung tissue. After EA intervention, the number of dead cells was markedly reduced, and the transcriptional levels of caspase-3/8 were decreased. Meanwhile, EA significantly upregulated the expressions of Axl, Mertk and Rac1, while downregulating that of Gas6.</p><p><strong>Discussion: </strong>These results indicate that EA exerts a lung-protective effect by inhibiting the inflammatory response and repairing damaged lung tissue of LPS-induced ALI rats. Efferocytosis function was suppressed in the LPS-induced ALI model. Whereas EA may enhance the efferocytotic function of lung tissue.</p><p><strong>Conclusion: </strong>EA intervention exerts significant protective effects against LPS-induced ALI in rats. This therapeutic benefit may be partially mediated by the activation of efferocytosis, thereby suggesting a novel mechanism for EA in ALI.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous COX-2 Expression in Breast Cancer: A Narrative Review of Immunohistochemical Studies.","authors":"Łukasz Kuźbicki","doi":"10.2174/0115665240510631260902105511","DOIUrl":"https://doi.org/10.2174/0115665240510631260902105511","url":null,"abstract":"<p><strong>Introduction: </strong>Induced Cyclooxygenase-2 (COX-2) can support cancer progression through various mechanisms and may be useful in predicting outcomes. COX-2 inhibitors are considered to have chemopreventive and therapeutic potential. This review aimed to verify the frequency of COX-2 immunohistochemical expression in breast cancer and its prognostic significance.</p><p><strong>Methods: </strong>The results for a total of 13,923 breast carcinomas from 60 publications were analyzed. A meta-analysis of COX-2 expression and overexpression frequency, an analysis of correlations with prognostic factors, and a cluster analysis of studies with similar results were conducted.</p><p><strong>Results: </strong>The median and mean values of the fraction of COX-2-positive cases across 34 studies, regardless of expression intensity, were 81% and 77±20%, respectively. COX-2 overexpression was demonstrated by 37 researchers, with median and mean frequencies of 49% and 49±15%, respectively. However, the results were highly heterogeneous (I2>90%, P < 0.0001). COX-2 was generally uncorrelated with clinical, pathological, and molecular prognostic factors and was associated with shorter patient survival in approximately half of the studies.</p><p><strong>Conclusion: </strong>The frequency of COX-2 expression in breast cancer is high but heterogeneous. COX-2 detected in epithelial cancer cells is a poorly effective prognostic and predictive marker. The discrepancies in the results may have both biological and methodological causes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative SEPT9 Methylation in Colorectal and Endometrial Cancers Suspected of Lynch Syndrome.","authors":"Sarawut Chanta, Pawana Panomket, Worrawit Wanitsuwan, Surasak Wanram","doi":"10.2174/0115665240483768260902064538","DOIUrl":"https://doi.org/10.2174/0115665240483768260902064538","url":null,"abstract":"<p><strong>Introduction: </strong>Lynch syndrome (LS) is associated with increased risks of colorectal cancer (CRC), endometrial cancer (EC), and other malignancies. This exploratory study evaluated quantitative SEPT9 promoter methylation in archived tumor tissue and whole blood from patients with suspected LS.</p><p><strong>Methods: </strong>In this retrospective observational study with cross-sectional molecular analysis, DNA from 22 paired formalin-fixed paraffin-embedded (FFPE) tumors and 22 matched EDTA whole-blood specimens (17 CRC and 5 EC) was analyzed. Methylation at five SEPT9 CpG sites was quantified by bisulfite pyrosequencing following nested PCR amplification. Tissue-blood methylation-status concordance was assessed descriptively using a ≥5% threshold.</p><p><strong>Results: </strong>Whole-blood SEPT9 methylation was higher in CRC than in EC (P<0.01), with relatively prominent signals at CpG2 and CpG4. Tissue-blood concordance was 59.1% overall (13/22), 58.8% in CRC (10/17), and 60.0% in EC (3/5). Within CRC, concordance was 16.7% in early-stage disease (1/6) and 66.7% in advanced-stage disease (8/11). These findings were exploratory and descriptive.</p><p><strong>Discussion: </strong>The observed stage-related pattern and tissue-blood concordance support further investigation of quantitative SEPT9 methylation as a complementary marker. The small cohort and exploratory nature of the thresholds preclude conclusions regarding diagnostic or prognostic performance.</p><p><strong>Conclusion: </strong>Quantitative SEPT9 methylation was detectable in archived FFPE tumors and whole blood from LS-suspected patients. Larger prospective studies are required to validate the observed differences and determine their clinical relevance.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"74th ASMS Conference on Mass Spectrometry, San Diego, 2026: A Special Focus on Molecular Medicine.","authors":"András Guttman","doi":"10.2174/0115665240535568260902114840","DOIUrl":"https://doi.org/10.2174/0115665240535568260902114840","url":null,"abstract":"","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid Profiling And The Effect Of SRGAP2 (Rs2580520) Polymorphism on The Serum Lipid Levels In Multiple Psychiatric Disorders In The Pakistani Population.","authors":"Aisha Nasir Hashmi, Zehra Agha, Rizwan Taj, Fatima Aftab, Raheel Qamar, Jamal B Williams, Maleeha Azam","doi":"10.2174/0115665240407814260407111430","DOIUrl":"https://doi.org/10.2174/0115665240407814260407111430","url":null,"abstract":"<p><strong>Introduction: </strong>The link between lipid profiles and various neuropsychiatric conditions has been studied; however, few studies have systematically pooled data to examine comparative associations between lipid components and multiple psychiatric conditions. Therefore, the current study aimed to conduct a comparative analysis of lipid components, their relationship with suicidality, and the effect of the SRGAP2 (rs2580520) polymorphism on serum lipid levels in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SHZ) in the Pakistani population.</p><p><strong>Methods: </strong>The rs2580520 was genotyped using the tetra-amplification refractory mutation system-PCR (TETRA-ARMS-PCR), and the CHOD/POD (Cholesterol oxidase/Peroxidase) method was used for serum lipid profiling.</p><p><strong>Results: </strong>A significant association of the rs2580520 risk allele (C) with suicidality in MDD (p<0.01) was found. Significantly lower levels of total cholesterol (TCH), highdensity lipids (HDL), and low-density lipids (LDL) were observed in MDD, BD, and SHZ (p<0.05). However, significantly elevated total lipid (TL) levels were observed in MDD (p<0.05) and lower TL levels in BD (p<0.05) compared to controls. This study also observed significantly lower serum TCH, LDL, HDL, and TL levels in the suicidal BD group (p<0.05).</p><p><strong>Discussion: </strong>The findings of this study support the hypothesis that the variation in lipid levels is associated with MDD, BD, and SHZ. The lower lipid component levels may serve as a potential biomarker of suicidality in BD, while the elevated serum TL levels may be linked to MDD.</p><p><strong>Conclusion: </strong>The study findings highlight the potential role of lipid component levels as biomarkers in psychiatric conditions, although further longitudinal studies are required to clarify causal relationships.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted NGS of Preoperative Circulating Cell-Free DNA in Colorectal Cancer.","authors":"Mária Škereňová, Erika Halasova, Miroslava Šarlinová, Dusan Loderer, Marian Grendar, Dana Dvorská, Katarína Tobiášová, Daniel Cierny, Juraj Miklušica, Miroslav Slezák, Peter Mikolajčík, Martin Grajciar","doi":"10.2174/0115665240518075260903095000","DOIUrl":"https://doi.org/10.2174/0115665240518075260903095000","url":null,"abstract":"<p><strong>Introduction: </strong>Circulating tumor DNA is a promising noninvasive tool for tumor genotyping and recurrence monitoring in Colorectal Cancer (CRC), but its role in nonmetastatic disease remains unclear. This cross-sectional study evaluated preoperative plasma circulating cell-free DNA (cfDNA) in patients undergoing complete mesocolic excision (CME) with D3 lymphadenectomy.</p><p><strong>Methods: </strong>Preoperative plasma samples were collected from 32 patients with predominantly right-sided CRC; 31 with histologically confirmed malignancy were analysed. cfDNA was sequenced using the AVENIO ctDNA Expanded Panel targeting 77 cancer-related genes. Sequencing metrics, Variant Allele Frequency (VAF), variant types, and cfDNA variants were evaluated.</p><p><strong>Results: </strong>High-quality cfDNA was obtained from all patients (mean yield 0.69 ng/μL). Sequencing met performance criteria (>22 million read pairs, >86% mapped reads, depth 6779×/3523×). Variants were detected in 74% of the patients, most frequently in TP53 (n=11), APC (n=8) and KRAS (n=7). The mean VAF was 0.8%, with some variants exceeding 20%. The most frequent hotspot was KRAS c.38G>A (p.Gly13Asp) (n=4). Recurrent variants were observed in IDH2, MET, GNAS, CTNNB1, and PDCD1LG2, indicating molecular heterogeneity.</p><p><strong>Discussion: </strong>Preoperative tumor-naïve cfDNA sequencing enabled detection of established CRC driver alterations and rare variants, supporting its potential for minimally invasive molecular characterization. Compared with tumor-informed approaches, this strategy allows plasma profiling without prior tissue sequencing; however, variant interpretation remains limited without matched tumor and white blood cell DNA.</p><p><strong>Conclusion: </strong>Targeted cfDNA sequencing is feasible in preoperative CRC patients undergoing CME and provides a molecular baseline for future perioperative studies. Larger prospective cohorts with longitudinal follow-up are required to define its prognostic and clinical utility.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non-coding RNA HOTAIR Drives Breast Cancer Progression Through miR-3619-5p/MGAT5 Axis.","authors":"Juan Guo, Meihong Cai, Chen Xu, Junli Fan, Shiqi Li, Qian Zhou, Xiaosi Yu, Wenjie Huang, Xinghua Long","doi":"10.2174/0115665240468538260903102004","DOIUrl":"https://doi.org/10.2174/0115665240468538260903102004","url":null,"abstract":"<p><strong>Introduction: </strong>HOX Transcript Antisense Intergenic RNA (HOTAIR) is a long-noncoding RNA that plays important roles in tumorigenesis. However, the underlying molecular mechanism of HOTAIR in breast cancer is not fully understood.</p><p><strong>Methods: </strong>In this study, high-throughput sequencing was carried out to analyze breast cancer transcriptomic changes after HOTAIR was overexpressed in MCF-7 cells. Gain- and loss-of-function assays were used to examine the effects of HOTAIR on the progression of breast cancer. A double-luciferase reporter assay was used to verify the possible correlation among HOTAIR, miR-3619-5p, and MGAT5.</p><p><strong>Results: </strong>We found that HOTAIR was overexpressed in breast cancer tissues and was related to the prognosis of breast cancer patients. Overexpression of HOTAIR promoted the proliferation, migration, and invasion of breast cancer cells. MiR-3619-5p was downregulated, and MGAT5 was upregulated in HOTAIR-overexpressing breast cancer cells compared with the negative cells. MiR-3619-5p was verified to be the target of HOTAIR, and MGAT5 was identified as a target of miR-3619-5p. MiR-3619- 5p rescued the effect of HOTAIR on the proliferation of breast cancer cells. MGAT5 silencing inhibited the proliferation of breast cancer cells. In addition, high-throughput sequencing indicated that HOTAIR overexpression altered the whole transcriptome of breast cancer.</p><p><strong>Discussion: </strong>Our findings suggested that HOTAIR may drive breast cancer progression through the miR-3619-5p/MGAT5 axis.</p><p><strong>Conclusion: </strong>HOTAIR might be a potential therapeutic target for breast cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-Encapsulated Aprepitant Enhances Anticancer Potency in Lung Cancer Cells.","authors":"Elif Kaya-Tilki, A Alper Öztürk, Selin Engür-Öztürk","doi":"10.2174/0115665240511001260831114038","DOIUrl":"https://doi.org/10.2174/0115665240511001260831114038","url":null,"abstract":"<p><strong>Introduction/objective: </strong>The repurposing of aprepitant (APR), a clinically approved NK-1R antagonist, represents a promising anticancer strategy; however, its rapid systemic clearance limits its therapeutic efficacy. This study aimed to design and systematically evaluate PLGA- and ERS-based APR nanoparticles, characterizing their physicochemical properties, assessing their anticancer potency, and investigating their specific impact on macrophage-mediated tumor invasion using an in vitro lung cancer model.</p><p><strong>Methods: </strong>APR-loaded poly(lactic-co-glycolic acid) (PLGA-APR) and Eudragit® RS 100 (ERS-APR) nanoparticles were prepared and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. In vitro drug release profiles were evaluated over 24 h. Antiproliferative activity was assessed in A549 lung cancer cells and THP-1 macrophages. A co-culture model with M2c-polarized THP-1 macrophages was used to investigate the effects on cancer cell invasion. Apoptosisrelated gene expression was analyzed to explore the underlying mechanisms.</p><p><strong>Results: </strong>Nanoparticles exhibited sizes ranging from 186-244 nm, low polydispersity indices, and high encapsulation efficiencies, with distinct surface charges. Sustained drug release over 24 h was observed, whereas free APR dissolved rapidly. Nanoencapsulation enhanced antiproliferative activity, with PLGA-APR showing a lower IC₅₀ at 48 h compared with free APR, and demonstrated tumor-selective cytotoxicity. Additionally, the nanoparticle formulations reduced M2c macrophage-induced invasion and increased the expression of apoptosis-related genes, including TNF-α, CASP8, and CASP3.</p><p><strong>Discussion: </strong>These findings suggest that nanoparticle-based delivery enhances the therapeutic potential of APR by improving its antitumor activity and limiting macrophage-mediated pro-tumor interactions.</p><p><strong>Conclusion: </strong>PLGA- and ERS-based APR nanoparticles demonstrated enhanced anticancer activity and represent a promising nanoparticle-based drug repurposing strategy for lung cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl Hydrocarbon Receptor Activation Prevents Lung Ischemia Reperfusion Injury by Inhibiting ROS-triggered Ferroptosis in Mice.","authors":"Peng Deng, Guanghua Xu, Li Wan, Jianwei Xu, Zuhuan Yao, Quanchao Sun","doi":"10.2174/0115665240399984251209163403","DOIUrl":"https://doi.org/10.2174/0115665240399984251209163403","url":null,"abstract":"<p><strong>Introduction: </strong>Lung ischemia-reperfusion injury (LIRI) is a serious complication of lung transplantation that causes respiratory distress and is associated with high mortality. Ferroptosis, a novel form of programmed cell death, contributes to the pathogenesis of LIRI. The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor that regulates a variety of physiological functions. However, the role and mechanism of AhR in ferroptosis during LIRI after lung transplantation remain to be further investigated.</p><p><strong>Materials and methods: </strong>AhR signaling and ferroptosis were examined in a mouse LIRI model and a pulmonary vascular endothelial cell line following hypoxiareoxygenation (H/R) culture. The severity of LIRI was assessed based on histological architecture and cytokine levels. Cell viability and damage were evaluated using the CCK-8 and LDH assays. Ferroptosis biomarkers, including Fe²⁷, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH), were measured using respective assay kits. PTGS2 (Prostaglandin-Endoperoxide Synthase 2), SLC7A11 (Solute Carrier Family 7 Member 11), and GPX4 (Glutathione Peroxidase 4) were analyzed by western blot. In vitro, lipid peroxidation was assessed by flow cytometry after DCFH-DA labeling. Transmission electron microscopy was used to observe mitochondrial ultrastructure.</p><p><strong>Results: </strong>Enhanced transcription of AhR and its downstream targets, CYP1A1 (Cytochrome P450 1A1) and CYP1B1 (Cytochrome P450 1B1), was observed. AhR deficiency exacerbated LIRI-induced ferroptosis and lung injury, whereas AhR activation mitigated lung injury and ferroptosis. H/R-induced cell injury and ferroptosis were alleviated by AhR activation. Increased ROS formation, primarily mitochondrial ROS (Mito-ROS), was triggered by AhR ablation or antagonism, and ROS inhibition subsequently reduced cell damage and ferroptosis.</p><p><strong>Discussion: </strong>Our findings indicate that AhR activation functions upstream by directly inhibiting excessive ROS accumulation triggered by I/R. This reduction in cellular oxidative stress prevents the lethal lipid peroxidation that drives ferroptosis.</p><p><strong>Conclusion: </strong>This study demonstrates the protective effect of AhR activation in LIRI by inhibiting ROS-induced ferroptosis, suggesting it may be a promising target for clinical prevention of LIRI.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}