Journal of Inflammation Research最新文献

{"title":"Association of the C-Reactive Protein-Triglyceride-Glucose Index with Kidney Injury in Patients with Coronary Heart Disease: A Two-Center Cross-Sectional Study.","authors":"Mengmeng Fan, Xueping Zhang, Xianwei Tian, Keli Li, Zhiqiang Liu","doi":"10.2147/JIR.S644335","DOIUrl":"https://doi.org/10.2147/JIR.S644335","url":null,"abstract":"<p><strong>Background: </strong>The composite index of inflammation and insulin resistance (IR), the C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), has been suggested to be closely associated with cardiovascular disease. However, the relationship between the CTI and kidney injury (KI), including its subtypes [declined kidney function (DKF) and proteinuria], remains unclear in patients with coronary heart disease (CHD), and whether sex differences exist is unknown.</p><p><strong>Methods: </strong>This two-center cross-sectional study enrolled 3793 patients with CHD between September 2021 and May 2026. Multivariable stepwise-adjusted logistic regression assessed associations of the CTI with KI and its subtypes. Restricted cubic spline (RCS) analysis identified dose-response relationships and threshold effects, followed by piecewise comparisons. Subgroup analyses stratified by sex were performed to evaluate consistency across sexes. The area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and the Boruta algorithm compared the discriminative performance of the CTI versus CRP and TyG alone for KI and its subtypes.</p><p><strong>Results: </strong>Multivariable logistic regression showed that the CTI was significantly associated with KI and its subtypes in CHD patients. The overall prevalence of KI was 814/3,793 (21.5%). RCS revealed that CTI exceeding 4.8, 4.7, and 4.55, respectively, significantly increased risks of KI, DKF, and proteinuria. Notably, the increased risk of KI was particularly evident when CTI exceeded 4.45 in females and 4.96 in males. AUC, DCA, and Boruta rankings all confirmed stronger discriminative performance of the CTI than CRP or TyG alone for KI and its subtypes.</p><p><strong>Conclusion: </strong>Elevated CTI was independently associated with KI and its subtypes in CHD patients, with clear threshold effects that differed by sex and superior discriminative performance to single indicators. These associations were more pronounced in overweight/obese patients. Although CTI may help identify individuals at higher risk, the sex-specific thresholds should be regarded as exploratory threshold estimates and require external validation before clinical application.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"644335"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182101","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":"Zebrafish Models of Arthritis and Their Applications in Traditional Chinese Medicine Screening: Advances and Perspectives.","authors":"Jialu Luo, Min Gao, Xianglu Li, Xiang Guo, Huilian Huang, Xiaoqiang Hou, Zhigang Mei, Zhitao Feng","doi":"10.2147/JIR.S629102","DOIUrl":"https://doi.org/10.2147/JIR.S629102","url":null,"abstract":"<p><p>The zebrafish is a widely utilized model organism in medical research because of its high reproductive capacity, rapid development, transparent embryos, genetic tractability, and similarity to humans in skeletal development. In this review, we searched CNKI and PubMed up to July 30, 2026 using combinations of \"zebrafish\", \"arthritis\", \"osteoarthritis\", \"rheumatoid arthritis\", \"gouty arthritis\", \"infectious arthritis\", \"traditional Chinese medicine\", and \"natural products\". Both Chinese and English articles were considered. A total of 67 articles were initially retrieved. After manual screening against the inclusion criteria, the most relevant studies were selected for this review. Studies were reviewed when they described zebrafish arthritis-related models, inflammatory or skeletal phenotypes, or TCM/natural product screening. Current research has applied zebrafish models mainly to osteoarthritis (OA) and rheumatoid arthritis (RA), while infectious and gouty arthritis models remain less developed. These models help elucidate pathogenic genes associated with OA, evaluate induced OA-like pathology, explore immune and vascular mechanisms in RA, simulate acute gout-related innate inflammation, and investigate host-pathogen responses relevant to infectious arthritis. Compared with previous reviews, this review specifically addresses the application of zebrafish arthritis models in traditional Chinese medicine (TCM) screening, with emphasis on model classification and current limitations. TCM compounds and formulas can be evaluated in zebrafish through whole-organism phenotypes including inflammatory-cell recruitment, angiogenesis, toxicity, and drug-response patterns. These findings demonstrate anti-angiogenic activities that may be relevant to arthritis, but they do not establish therapeutic efficacy against arthritis itself. Future studies should further refine zebrafish models for specific arthritis types, report strain background and dose more consistently, and validate larval screening results in adult zebrafish or mammalian models when possible, as zebrafish are complementary screening models that cannot fully reproduce all aspects of adult human arthritis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"629102"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182278","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":"Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.","authors":"Chun Wang, Fu Shuying, Jin Jing, Fang Fuquan, Jie Huang","doi":"10.2147/JIR.S654590","DOIUrl":"https://doi.org/10.2147/JIR.S654590","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome characterized by concurrent inflammation, immunosuppression, endothelial dysfunction and metabolic failure. Although current immunometabolic research primarily focuses on glycolysis, mitochondrial respiration and lipid metabolism, nucleotide metabolism links biosynthesis, redox homeostasis, epigenetic regulation and extracellular danger signalling. This Review synthesizes evidence for altered purine and pyrimidine synthesis, ribonucleotide reduction, nucleoside salvage and purinergic signalling across immune-cell populations in sepsis. We distinguish clinical observations from mechanistic evidence in experimental sepsis and hypotheses extrapolated from cancer or immune-mediated disease. Human observational studies support involvement of the extracellular ATP-CD39/CD73-adenosine axis in sepsis, while experimental studies provide complementary mechanistic evidence. By contrast, the roles of DHODH, RRM2 and the uridine-UPP1 salvage pathway remain predominantly preclinical, particularly in ferroptosis and acute organ injury. We propose that nucleotide metabolism functions as a time-, cell- and compartment-dependent regulatory network rather than a uniformly activated pathway. Clinical translation will require longitudinal metabolite-enzyme-receptor profiling, isotope-resolved flux analysis, spatial and single-cell approaches, and biomarker-defined therapeutic windows. Such strategies may enable nucleotide-directed interventions to complement antimicrobial treatment and organ support without compromising protective immunity.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"654590"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182313","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":"Electrical Impedance Tomography-Informed Regional Functional Phenotypes in Sepsis-Associated Acute Respiratory Distress Syndrome.","authors":"Hangbo Hu, Jin Qian, Hongsheng Deng, Kun Chen, Xinyong Liu","doi":"10.2147/JIR.S644978","DOIUrl":"https://doi.org/10.2147/JIR.S644978","url":null,"abstract":"<p><p>Sepsis-associated acute respiratory distress syndrome (SA-ARDS) is a heterogeneous syndrome in which systemic inflammation, vascular dysfunction, altered fluid balance, chest-wall loading, and respiratory effort may produce regional abnormalities not captured by global respiratory variables. Electrical impedance tomography (EIT) provides continuous bedside assessment of regional ventilation and, increasingly, regional perfusion. This review summarizes EIT-derived measures relevant to SA-ARDS and examines how key sepsis-associated mechanisms may influence regional ventilation, perfusion, and mechanics. Six candidate functional patterns are proposed: collapse-shunt dominance, overdistension-dead-space dominance, perfusion-defect dominance, diffuse low aeration with limited recruitability, abdominal pressure-diaphragm interaction, and effort-related regional asynchrony. These patterns are neither mutually exclusive nor specific to SA-ARDS and may evolve over time.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"644978"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182245","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":"Between Fire and Restraint: Context-Dependent Roles of Interleukins 27, 33, 35 and 37 in Acute Pancreatitis.","authors":"Serge Chooklin, Serhii Chuklin","doi":"10.2147/JIR.S643664","DOIUrl":"https://doi.org/10.2147/JIR.S643664","url":null,"abstract":"<p><strong>Background: </strong>Interleukins 27 (IL-27), 33 (IL-33), 35 (IL-35) and 37 (IL-37) occupy potentially important but biologically non-equivalent positions at the interface between inflammatory amplification, tissue protection and immune restraint in acute pancreatitis (AP). This narrative review critically synthesizes AP-specific evidence, distinguishing mechanistic participation from biomarker association and defining translational priorities.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Scopus and Google Scholar were searched through July 2026. The review was structured with reference to the Scale for the Assessment of Narrative Review Articles (SANRA). Of 215 records identified, 43 underwent full-text assessment and 35 were included in the narrative synthesis (32 original studies and 3 reviews). Primary AP studies were prioritized, with landmark mechanistic studies used to interpret cytokine biology.</p><p><strong>Results: </strong>IL-33/ST2 was the most extensively studied axis and showed phase-, compartment- and molecular-form-dependent effects. Soluble ST2 correlated with severity but has not been validated for incremental prediction. IL-37 had the strongest direct protective evidence, inhibiting NLRP3-caspase-1-gasdermin D-mediated acinar-cell pyroptosis experimentally and showing an inverse association with pancreatic necrosis in patients; however, this clinical association derived from a single cohort and requires external validation. IL-35 findings were contradictory, with both severity-associated increases and reduced concentrations reported; assay characteristics may limit reliable distinction of intact bioactive IL-35 from free subunits or related complexes. Evidence for IL-27 was sparse and largely indirect. Across all four cytokines, clinical evidence remains limited by small or heterogeneous cohorts, inconsistent timing and analytical methods, and insufficient independent validation.</p><p><strong>Conclusion: </strong>These cytokines should not be considered a uniform anti-inflammatory group. IL-33/ST2 is context-dependent, IL-37 is a promising but preclinical cytoprotective candidate, and IL-35 and IL-27 remain hypothesis-generating. None is validated as a stand-alone biomarker or therapeutic target for routine AP care. Further progress requires standardized assays, longitudinal sampling and independent clinical validation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"643664"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182104","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":"KLF4 Protects Against Sepsis-Induced Coagulopathy via Inhibition of the AKT/mTOR/STAT3 Signaling Pathway.","authors":"Rongrong Zhang, Yun Hong, Darong Hai, Hongyan Du, Liwen Zhao, Zhengyan Li, Fangkai Yin, Wanli Zheng, Kaicheng Wang, Jingye Pan, Yueyue Huang","doi":"10.2147/JIR.S642803","DOIUrl":"https://doi.org/10.2147/JIR.S642803","url":null,"abstract":"<p><strong>Purpose: </strong>Coagulation dysfunction is an independent predictor of morbidity and mortality in patients with severe sepsis, yet current therapeutic options remain inadequate. This study systematically evaluated the therapeutic potential of Krüppel-like factor 4 (KLF4) in sepsis-induced coagulopathy and explored the underlying molecular mechanisms.</p><p><strong>Methods: </strong>In vivo, mice were randomized into sham operation group, cecal ligation and puncture (CLP) group, and CLP + APTO-253 groups. The KLF4 agonist APTO-253 was intraperitoneally administered to CLP-induced septic mice to evaluate systemic inflammation, coagulation dysfunction, acute lung injury, and survival outcomes. In vitro, RAW264.7 macrophages were assigned to six core treatment groups: control group, APTO-253 group, LPS group, LPS + APTO-253 group, LPS + KLF4 overexpression group, and LPS + KLF4 knockdown group. Cellular inflammatory responses, coagulation-related biomarkers, and AKT/mTOR/STAT3 pathway activity were detected.</p><p><strong>Results: </strong>In vivo, APTO-253 treatment significantly attenuated systemic inflammation and coagulopathy in septic mice via the upregulation of KLF4, accompanied by reduced levels of proinflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α)) and coagulation-related biomarkers (fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1)). This therapeutic intervention ameliorated pathological manifestations, including pulmonary tissue damage, macrophage infiltration, and fibrin deposition, ultimately enhancing survival. In vitro, both APTO-253 treatment and KLF4 overexpression suppressed LPS-induced IL-6, IL-1β, TNF-α, TF, and PAI-1 through the inhibition of the AKT/mTOR/STAT3 signaling pathway. Conversely, KLF4 knockdown potentiated LPS-induced hyperactivation of this pathway, resulting in amplified proinflammatory and procoagulant responses.</p><p><strong>Conclusion: </strong>KLF4 overexpression ameliorates sepsis-induced coagulation dysfunction by inhibiting AKT/mTOR/STAT3 signaling. Thus, KLF4 represents a potential therapeutic target for coagulopathy in sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"642803"},"PeriodicalIF":4.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167523","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":"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}