Journal of Inflammation Research最新文献

{"title":"HMGCS2 Palmitoylation Promotes Diabetes-Induced Erectile Dysfunction Through PPARα-Mediated Macrophage Extracellular Trap Formation.","authors":"Chaohong Zhang, Guangjie Li, Lixing Jiang, Huilong Fang, Haiqing Fan, YuYe Wu","doi":"10.2147/JIR.S623377","DOIUrl":"https://doi.org/10.2147/JIR.S623377","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus-induced erectile dysfunction (DMED) is a prevalent complication with limited therapeutic options for non-responders to conventional treatments. Macrophage extracellular traps (METs) are implicated in various pathologies, but their role and regulatory mechanisms in DMED remain unclear. This study investigates the role of HMGCS2 palmitoylation in promoting MET formation and DMED pathogenesis through PPARα interaction.</p><p><strong>Methods: </strong>In vitro models were established using RAW264.7 macrophages treated with high glucose (HG) and palmitic acid (PA). A DMED rat model was induced by high-fat diet and streptozotocin injection, followed by administration of the palmitoylation inhibitor CMA (cyano-myracrylamide). HMGCS2 palmitoylation, protein expression, and its interaction with PPARα were assessed using acyl-biotin exchange (ABE) and co-immunoprecipitation (Co-IP) assays. MET formation, reactive oxygen species (ROS) production, oxidative stress markers (MDA, GSH), mitochondrial function (MMP, ATP, morphology), macrophage infiltration, and cell apoptosis were evaluated via Western blot, immunofluorescence, ELISA, transmission electron microscopy, flow cytometry, and TUNEL staining. Erectile function was assessed in vivo by apomorphine-induced penile erection tests.</p><p><strong>Results: </strong>HMGCS2 expression and palmitoylation were significantly upregulated in both HG/PA-treated macrophages and corpus cavernosum of DMED rats. CMA treatment effectively reduced HMGCS2 palmitoylation, attenuated its interaction with PPARα, and downregulated HMGCS2 expression. Consequently, pharmacological inhibition of palmitoylation suppressed HG/PA-induced MET formation, ROS overproduction, oxidative stress, and mitochondrial dysfunction in vitro. In DMED rats, CMA administration significantly improved penile erectile function, which recovered to 78% of the number of erections of the control group per unit time, as well as reduced peripheral blood PA levels, and alleviated pathological changes in corpus cavernosum. Furthermore, CMA inhibited MET formation, reduced macrophage infiltration, suppressed ROS and oxidative stress, and decreased cell apoptosis in vivo.</p><p><strong>Conclusion: </strong>Our findings demonstrate that HMGCS2 palmitoylation drives DMED pathogenesis by promoting MET formation through enhanced PPARα interaction. Targeting HMGCS2 palmitoylation represents a promising therapeutic strategy for DMED.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"623377"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166008","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}

{"title":"The Role of TXNIP in Skeletal Muscle Physiology and Related Diseases: Current Perspectives.","authors":"Jiazhe Du, Xudong Gao, Sai Yao, Ludan Zhang","doi":"10.2147/JIR.S637774","DOIUrl":"https://doi.org/10.2147/JIR.S637774","url":null,"abstract":"<p><p>Thioredoxin-interacting protein (TXNIP) is a multifunctional regulatory protein of the α-arrestin family that acts as a redox sensor, an energy-responsive molecule, and a transcription-associated regulator. TXNIP has emerged as a key regulator of skeletal muscle homeostasis and has been implicated in the pathogenesis of multiple muscle disorders. Skeletal muscle is a principal site of systemic glucose disposal, accounting for more than 70% of insulin-stimulated glucose uptake in the human body. TXNIP has been implicated in sarcopenia, obesity-related insulin resistance, limb ischemia-induced muscle injury, disuse muscle atrophy, and hereditary muscular dystrophy through multiple mechanisms, including glutathione metabolic regulation, ferroptosis, NLRP3 inflammasome activation, impaired GLUT4 membrane translocation, and altered mitochondrial substrate oxidation. Recent advances in gene editing, single-cell sequencing, metabolomics, and human clinical research have enabled a more detailed characterization of TXNIP-related molecular mechanisms in skeletal muscle. This review provides a systematic synthesis of recent evidence on TXNIP in skeletal muscle, organized around seven themes: its molecular characteristics, expression and regulatory patterns in skeletal muscle, physiological functions, disease-specific pathogenic mechanisms, intervention-related regulatory networks, current limitations, and future perspectives. This review aims to provide a mechanistic rationale for targeting TXNIP as a potential strategy for the prevention and treatment of skeletal muscle-related diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"637774"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164690","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}

{"title":"Traditional Chinese Medicine Modulation of Macrophage Polarization in Inflammation Associated with Coronary Heart Disease: Mechanisms and Challenges.","authors":"Shuai Wang, Dongshuai Zhang, Yandan Yang, Yang Li, Huijie Zhang, Bing Wang, Deyou Jiang","doi":"10.2147/JIR.S639064","DOIUrl":"https://doi.org/10.2147/JIR.S639064","url":null,"abstract":"<p><p>Coronary heart disease (CHD) remains a leading cause of global mortality, with unresolved inflammation constituting a major residual risk after conventional therapies. Macrophage polarization, characterized by shifts between pro-inflammatory M1 and reparative M2 phenotypes, influences vascular inflammation, plaque stability, myocardial injury, and tissue repair, making it a potential therapeutic target in CHD. Traditional Chinese Medicine (TCM) is increasingly recognized for its multi-target immunomodulatory properties. This review systematically synthesizes the current evidence on the mechanisms by which TCM formulas and active ingredients regulate macrophage polarization to modulate the inflammatory response in CHD. Importantly, the stage-specific roles of TCM during the progression of CHD (atherosclerosis, acute myocardial infarction, ischemia-reperfusion injury, and post-infarct repair) are delineated. Emerging mechanistic insights into metabolic reprogramming, mitochondrial function, and epigenetic modifications are also highlighted. However, most evidence linking TCM to macrophage polarization in CHD is derived from cellular and animal studies, while direct clinical validation remains limited. Finally, current limitations, knowledge gaps, and future directions for basic research and clinical translation are discussed. By moving beyond descriptive pathway enumeration to an integrated framework that encompasses signaling networks, disease-stage dynamics, and deep molecular mechanisms, this review aims to provide a comprehensive reference for investigators and clinicians interested in TCM-based immunomodulatory strategies for CHD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"639064"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168614","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}

{"title":"Hydroxygenkwanin Identified in Rehmanniae Radix Praeparata-Corni Fructus Ameliorates Postmenopausal Osteoporosis via Modulation of the AGE-RAGE Signaling Pathway.","authors":"Songlin Liang, Dezhi Tang, Hui Wang, Shang Gao, Zenghui Tian, Xintian Qu, Luming Kong, Xin Xin, Jiatong Li, Nianhu Li","doi":"10.2147/JIR.S608114","DOIUrl":"https://doi.org/10.2147/JIR.S608114","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) is a metabolic bone disease marked by reduced bone mass and compromised microarchitecture, increasing fragility fracture risk. The traditional Chinese herbal pair <i>Rehmanniae Radix Praeparata-Corni Fructus</i> (RRP-CF) is frequently used for OP, but its mechanism remains unclear.</p><p><strong>Methods: </strong>Network pharmacology, UHPLC-HRMS, molecular docking, and molecular dynamics simulations were integrated to identify the potential active components of RRP-CF and to predict the potential targets and related signaling pathways underlying its anti-osteoporotic effects. These predictions were further validated through in vitro (using 25 and 50 µM hydroxygenkwanin (HGK)) and in vivo experiments in ovariectomized (OVX) rats (using 10 and 20 mg/kg HGK).</p><p><strong>Results: </strong>UHPLC-HRMS identified HGK as one of the detectable components of RRP-CF. A total of 66 common targets between RRP-CF and OP were screened out by network pharmacology; Protein-Protein Interaction (PPI) network analysis showed that estrogen receptor 1 (ESR1), tumor protein p53 (TP53), tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), and prostaglandin-endoperoxide synthase 2 (PTGS2) were the key targets. Gene Ontology enrichment suggested that RRP-CF-associated targets were mainly involved in inflammatory response, and the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway was identified as a critical pathway. In vivo experiments confirmed that RRP-CF could improve bone microstructure and collagen content, as evidenced by increased BMD (from 106.58 ± 11.09 mg/cm³ in the OVX group to 188.35 ± 10.18 mg/cm³ in the 10 mg/kg HGK-treated group) and bone volume/tissue volume (BV/TV) (from 0.13 ± 0.02 to 0.29 ± 0.05). Mechanistically, HGK treatment downregulated RAGE expression in OVX rat bone tissue (<i>P</i> = 0.0208) and receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW264.7 cells (<i>P</i> = 0.0005), and suppressed osteoclast-related proteins including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) (<i>P</i> = 0.0061 in cells) and cathepsin K (CTSK) (<i>P</i> < 0.0001 in rats; <i>P</i> = 0.0006 in cells). Furthermore, rescue experiments using the RAGE inhibitor FPS-ZM1 suggested that the effects of HGK were associated with modulation of RAGE-related signaling.</p><p><strong>Conclusion: </strong>Our findings indicate that RRP-CF can inhibit bone loss in OVX rats, and suggest that HGK, as a potential active constituent of RRP-CF, may exert anti-osteoporotic effects through modulation of the AGE-RAGE pathway and downregulation of osteoclast-related proteins including p53, p-AKT, NFATc1 and CTSK. These findings provide a preliminary mechanistic basis for developing novel OP therapeutic regimens, though further pharmacokinetic and safety studies are warranted.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"608114"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165588","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}

{"title":"Time-Stable Ferroptosis-Related Candidate Genes in Myocardial Ischemia/Reperfusion Injury Identified by Multi-Time-Point Transcriptomic Analysis: Prioritization of NCF2 Through Public Datasets and AC16 Cell Validation.","authors":"Rong Huang, Jun Wang, Junchen He, Min Zhong","doi":"10.2147/JIR.S627947","DOIUrl":"https://doi.org/10.2147/JIR.S627947","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis contributes to myocardial ischemia/reperfusion injury (MIRI), but time-stable ferroptosis-related transcriptional features across reperfusion stages and their links to peripheral immune profiles remain unclear. This study aimed to identify time-stable ferroptosis-related candidates in MIRI using public datasets and AC16 hypoxia/reoxygenation experiments.</p><p><strong>Methods: </strong>GSE160516, containing reperfusion samples at 6 h, 24 h and 72 h, was used as the primary time-course dataset. Differential expression was analyzed with limma and intersected with FerrDb genes. Candidates were screened for directionally consistent changes, followed by three-time-point FDR filtering and deprioritization of broad inflammatory/tissue-injury-response genes. STRING was used for functional and interaction-network analyses. Directional support was assessed in GSE61592, and human PBMC relevance in GSE59867 with MCPcounter. AC16 cardiomyocytes underwent hypoxia/reoxygenation (H/R) with or without ferrostatin-1 (Fer-1) for ferroptosis-related phenotypic and molecular assessment.</p><p><strong>Results: </strong>Temporal screening yielded 149 candidates, of which 37 remained significant after FDR correction at all three reperfusion time points; deprioritization of seven broad inflammatory/tissue-injury-response genes yielded a 30-gene shortlist, from which ASNS, PSAT1, NCF2, PRKAA2, ULK1 and HIF1A were prioritized. Functional analyses implicated hypoxic response, oxidative stress, metabolic stress, autophagy and inflammation-related processes. In GSE59867 PBMCs, support varied across candidates, with NCF2 and ULK1 remaining significantly elevated in STEMI admission samples after BH correction, while MCPcounter suggested marked acute immune remodeling. In AC16 H/R cells, a ferroptosis-related injury phenotype was partially attenuated by Fer-1; NCF2 protein increased after H/R and was partially reduced by Fer-1.</p><p><strong>Conclusion: </strong>This study identified ferroptosis-related genes with sustained transcriptional changes during MIRI. NCF2 showed the most consistent support across datasets, sample types and AC16 H/R experiments, suggesting it as a prioritized candidate linking ferroptosis-related oxidative stress and myeloid immune activation. A causal role for NCF2 in ferroptosis remains to be established.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"627947"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165059","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}

{"title":"Clinical Phenotyping and Treatment - Related Considerations in the Prognostic Assessment of the BNP - to - Albumin Ratio [Letter].","authors":"Onur Akgün","doi":"10.2147/JIR.S658431","DOIUrl":"https://doi.org/10.2147/JIR.S658431","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"658431"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169701","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}

{"title":"The Use of Montelukast in Pediatric Asthma and Anti-Inflammatory Effects - Easy Choice or a Balancing Act?","authors":"Aleksander Adamiec, Katarzyna Karwowska, Katarzyna Moliszewska, Karolina Dumycz, Wojciech Feleszko","doi":"10.2147/JIR.S604913","DOIUrl":"https://doi.org/10.2147/JIR.S604913","url":null,"abstract":"<p><p>Montelukast is a selective cysteinyl leukotriene receptor 1 antagonist with an established, though nuanced, role in the management of asthma and allergic rhinitis. By inhibiting leukotriene-mediated signaling, montelukast targets a pathway involved in bronchoconstriction, mucus secretion, vascular permeability, eosinophil recruitment, cytokine release, and airway remodeling. Available evidence indicates that montelukast may reduce several markers of allergic inflammation, including fractional exhaled nitric oxide, peripheral and tissue eosinophilia, eosinophil-derived mediators, adhesion molecules, selected cytokines, and markers related to airway remodeling. These effects are most consistently demonstrated in asthma and allergic rhinitis, while evidence in chronic urticaria, atopic dermatitis, and other inflammatory conditions remains limited or exploratory. Montelukast's once-daily oral administration and age-adjusted pediatric formulations make it a practical option in selected children, particularly when inhaled therapy is difficult or adherence is problematic. However, montelukast should not be regarded as a direct substitute for corticosteroid-based anti-inflammatory therapy. Current evidence and guideline positioning support its use mainly as an add-on controller, or an alternative when more efficacious treatment is contraindicated. The benefit-risk balance is further shaped by concerns regarding neuropsychiatric adverse events, especially in children, although evidence remains heterogeneous. Current data show no increased risk of severe, diagnostically coded neuropsychiatric events, yet milder sleep-related and behavioral symptoms are consistently reported, so that caution and active monitoring remain warranted. Overall, montelukast remains a biologically plausible and clinically useful therapy, but its value depends on appropriate patient selection and realistic expectations of its anti-inflammatory potential.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"604913"},"PeriodicalIF":4.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169717","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}

{"title":"Targeting Inflammation in Osteoarthritis Pain: A Phenotype-Driven Approach.","authors":"Wei Zheng, Chuan Huang, Shen Liu, Kai Fu","doi":"10.2147/JIR.S614867","DOIUrl":"https://doi.org/10.2147/JIR.S614867","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a chronic joint disease marked by the progressive loss of articular cartilage and associated inflammatory processes, which can lead to significant pain and disability. However, the heterogeneous nature of OA has limited the effectiveness of many anti-inflammatory interventions, highlighting the need for phenotype-driven therapeutic strategies.</p><p><strong>Methods: </strong>This narrative review was conducted by searching PubMed, Web of Science, and Google Scholar from inception to June 2025. Predefined keywords included \"osteoarthritis\", \"inflammation\", \"pain\", \"synovitis\", \"effusion\", \"treatment\", \"therapy\" and \"clinical trials\". Additional relevant publications were identified through citation tracking of the included papers.</p><p><strong>Results: </strong>Our analysis of recent randomized clinical trials (RCTs) reveals a clear divergence in therapeutic efficacy, while targeted biologics (eg, TNF-α inhibitors like adalimumab and IL-1 blockers such as lutikizumab) have largely failed to meet primary pain endpoints in unselected populations, broad-spectrum immunomodulators like methotrexate (MTX) show significant promise, particularly in reducing pain and stiffness for the inflammatory phenotype. Furthermore, emerging evidence suggests that intra-articular (IA) treatments and phenotype-driven stratifications are essential to overcoming the current \"one-size-fits-all\" failure in OA drug development.</p><p><strong>Conclusion: </strong>The central message of this review is that the inconsistent efficacy of anti-inflammatory therapies in OA reflects a patient-selection problem more than a failed target: agents tested in unselected populations, including most anti-cytokine biologics, have not relieved pain, whereas signals emerge for MTX in patients with an inflammatory phenotype. Stratifying patients by imaging-defined synovitis or effusion and inflammatory biomarkers is therefore the key unmet need, and phenotype-driven trial design-rather than new molecular targets alone-offers the most promising path to effective inflammation-targeted treatment of OA pain.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"614867"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164522","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}

{"title":"Ferroptosis Profiling of Outcome-Associated Monocyte Subsets and the Potential Regulatory Role of LDHA in Early Sepsis.","authors":"Xiaoye Wang, Dan Liu, Si Li, Kun Wang","doi":"10.2147/JIR.S633372","DOIUrl":"https://doi.org/10.2147/JIR.S633372","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis carries high morbidity and mortality, and early precise intervention is critical for improving outcomes. The heterogeneity of circulating immune cells, particularly at the monocyte subset level, remains a major barrier to early risk stratification. This study aimed to identify prognosis-associated monocyte subsets and their key regulators in early sepsis, providing potential clues for early prognostic assessment and targeted intervention.</p><p><strong>Methods: </strong>We analyzed single-cell transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from patients with early sepsis and healthy controls in the GSE167363 dataset to define myeloid subsets associated with clinical outcomes. Core regulatory molecules were prioritized by intersecting differentially expressed genes (DEGs) with cell death-related gene sets, and their expression patterns were examined in bulk transcriptomic cohorts. The lead candidate was further evaluated through in vitro functional experiments and in vivo survival studies using the cecal ligation and puncture (CLP) mouse model.</p><p><strong>Results: </strong>A transitional monocyte subset defined by high <i>CD14</i> and modest <i>FCGR3A</i> expression, positioned at the intermediate node of monocyte differentiation, was markedly depleted in sepsis non-survivors. Gene Set Enrichment Analysis (GSEA) revealed ferroptosis as the predominant cell death modality in this subset among non-survivors. Lactate dehydrogenase A (LDHA) was pinpointed as a core regulatory molecule, and its differential expression was validated in independent bulk transcriptomic cohorts. In vitro assays confirmed that LDHA inhibition attenuated ferroptosis in THP-1-derived macrophages. Consistently, both myeloid-specific <i>Ldha</i> conditional knockout (cKO) and pharmacological inhibition of LDHA markedly improved the 7-day survival of CLP-induced septic mice.</p><p><strong>Conclusion: </strong>This study identifies an outcome-associated monocyte subset with a ferroptosis signature in early sepsis and suggests a potential regulatory role for LDHA in monocyte ferroptosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"633372"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166620","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}

{"title":"Medicinal and Edible Plant-Derived Exosome-Like Nanovesicles: Promising Therapeutics and Drug Delivery Nanoplatforms.","authors":"Likang Liu, Fuji Yang, Yongmin Yan, Shihui Li","doi":"10.2147/JIR.S624415","DOIUrl":"https://doi.org/10.2147/JIR.S624415","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Medicinal and edible plant-derived exosome-like nanovesicles (MEPELNVs) have attracted considerable attention as naturally derived immunomodulatory nanoplatforms for inflammatory disease intervention, owing to their excellent biocompatibility, low immunogenicity, and abundant bioactive cargoes capable of regulating immune responses. While recent reviews have broadly surveyed plant-derived exosome-like nanovesicles (PELNVs) across diverse botanical sources or focused on general isolation technologies and drug delivery applications, a systematic synthesis that specifically centers on medicinal and edible plants and integrates isolation methodology with immunomodulatory functionality remains lacking. This review addresses this gap by concentrating on the unique dual identity of MEPELNVs that combines validated pharmacological heritage from traditional medicine with the safety profile of dietary sources, and examines how their immunomodulatory potential is shaped by upstream preparation techniques. As research has progressed, techniques for isolating and preparing these extracellular vesicles have diversified; however, significant challenges remain in improving purity, optimizing yield, and preserving their immunomodulatory and anti-inflammatory biological functions. This review comprehensively surveys current mainstream isolation and preparation methods, analyzes how each technique impacts vesicle integrity and immune-regulatory activity, and discusses their differential effects on inflammatory mediator release and immune cell functionality. Based on recent preclinical findings, we highlight the potential clinical applications of MEPELNVs in three inflammation-centric areas: first, reprogramming macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes to alleviate chronic inflammation; second, remodeling the tumor immune microenvironment by alleviating PD-L1-mediated immunosuppression; and third, ameliorating metabolic inflammation and promoting immune homeostasis in metabolic diseases. In summary, while MEPELNVs present considerable therapeutic opportunities across anti-inflammatory, anti-tumor, and metabolic disease intervention, their clinical translation is currently hindered by substantial challenges. These include the absence of standardized isolation and quality control protocols, batch-to-batch heterogeneity in vesicle yield and cargo composition, incomplete safety and toxicological profiling, poorly understood cross-kingdom regulatory mechanisms, and underdeveloped regulatory frameworks. This review critically discusses these translational barriers and proposes actionable strategies to overcome them, offering a realistic roadmap from bench to bedside. By comprehensively evaluating existing research progress, this review aims to provide theoretical support and practical technical guidance for advancing the clinical translation of MEPELNVs as novel anti-inflammatory therapeutics, ultimately promoting their bro","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"624415"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166106","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}