Journal of Inflammation Research最新文献

{"title":"Targeting Eosinophils in Asthmatic Inflammation: Benefits and Drawbacks.","authors":"David Broide","doi":"10.2147/JIR.S521238","DOIUrl":"10.2147/JIR.S521238","url":null,"abstract":"<p><p>Asthma is associated with eosinophilic airway inflammation which contributes to poor asthma outcomes in a subset of severe asthmatics. This review traces the scientific rationale as well as the clinical development of novel therapeutics to target either IL-5 or the IL-5α receptor to deplete eosinophils from the airway to improve asthma outcomes in severe asthma with eosinophilic airway inflammation. The importance of IL-5 to eosinophil growth, survival, and function was initially identified in mice, and has been confirmed in studies of human eosinophils. As both IL-5 and the IL-5α receptor were identified as therapeutic targets to deplete eosinophils in the airway in asthmatics, humanized IgG antibodies were developed to target either IL-5 or the IL-5α receptor in eosinophilic asthma. The current availability of three biologics that deplete eosinophils (mepolizumab, reslizumab, and benralizumab) has provided a novel therapeutic approach to treat severe asthma with eosinophilic inflammation not controlled by inhaled corticosteroids in combination with long acting bronchodilators. Two of these eosinophil targeted biologics (mepolizumab, reslizumab) target IL-5 an eosinophil growth factor, while the third eosinophil targeted biologic (benralizumab) targets the IL-5α receptor expressed by eosinophils. Each of these eosinophil targeted therapies significantly deplete eosinophils in the blood, sputum, and airway and are associated with a significant approximately 50% reduction in asthma exacerbations in most studies without significant side effects. In addition, selected studies have shown that eosinophil targeted biologics improve asthma symptom quality of life scores and lung function. At present, there are no direct head to head comparison studies to determine whether any of the three eosinophil targeted biologics has a better asthma outcome profile/safety profile. The development of eosinophil targeted biologics has been a significant advance in the treatment of severe asthma with eosinophilic inflammation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12421-12445"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064803","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":"Identification of Novel Biomarkers Associated with Corticosteroid Resistance in Asthma by Bioinformatics Analysis and Experimental Validation.","authors":"Lingling Xuan, Lulu Ren, Wen Zhang, Zhuoling An","doi":"10.2147/JIR.S527640","DOIUrl":"10.2147/JIR.S527640","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroid resistance in asthma, marked by reduced glucocorticoid response, is significantly influenced by cigarette smoke (CS). We sought to explore potential novel biomarkers and therapeutic targets associated with CS-induced corticosteroid resistance in asthma.</p><p><strong>Methods: </strong>GSE230048 (related to corticosteroid resistance) and GSE13896 (from CS-exposed macrophages) were obtained from GEO. Initially, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to discover key genes involved in corticosteroid resistance in asthma. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic accuracy of these markers. CIBERSORT was applied to clarify immune cell infiltration. Expression of the key biomarker was validated in asthma patients and asthma murine models.</p><p><strong>Results: </strong>Five overlapping genes upregulated in corticosteroid-resistant asthma patients and smokers' alveolar macrophages were identified. Subsequently, using WGCNA, the most relevant modules were identified and intersected with differentially expressed genes. Tensin 1 (TNS1), ATP-binding cassette subfamily C member 4 (ABCC4), and TNF receptor superfamily member 21 (TNFRSF21) were identified as critical biomarkers for corticosteroid resistance in asthma. ROC analysis showed an AUC of 0.718 for the three-marker combination. Single-cell RNA sequencing confirmed their expression in macrophages from asthmatic patients. Elevated levels of TNS1, ABCC4, TNFRSF21, and M2 macrophage markers (CD301 and CD206) were observed in CS-exposed murine lung tissues and CS condensate-treated Raw264.7 cells. TNS1 knockdown significantly reduced CD301 and CD206 expression, suggesting its role in promoting macrophage M2 polarization.</p><p><strong>Conclusion: </strong>In conclusion, we identified three hub genes (TNS1, ABCC4, and TNFRSF21) associated with CS-induced corticosteroid resistance in asthma. Additionally, TNS1 may be involved in CS-induced corticosteroid resistance in asthma by promoting macrophage M2 polarization.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12379-12400"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064868","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 Impact of the Trajectory of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio on the Incidence of Metabolic Dysfunction-Associated Fatty Liver Disease: Random Forest Anaylsis, Trajectory Anaylsis, and Mendelian Randomization Study.","authors":"Wenjing Zhang, Shuai Ji, Ren Chen, Nabao Chen, Xiaoshan Zhao, Dong Han, Ruiqing Dong, Zhaoting Hu","doi":"10.2147/JIR.S536635","DOIUrl":"10.2147/JIR.S536635","url":null,"abstract":"<p><strong>Background and aims: </strong>The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) has emerged as a novel biomarker integrating inflammation and lipid metabolism, but its longitudinal association with metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. This study aimed to investigate the impact of MHR trajectories on MAFLD risk using multidisciplinary approaches.</p><p><strong>Methods: </strong>We conducted a comprehensive anaylsis combining: (1) machine learning-based random forest modeling to evaluate feature importance; (2) prospective cohort anaylsis with repeated MHR measurements to identify trajectory patterns; and (3) Mendelian randomization (MR) to infer causality.</p><p><strong>Results: </strong>Three distinct MHR trajectories were identified in the cohort. Compared to the low-stable group, both moderate-increasing (HR 1.17, 95% CI 1.04-1.32) and high-fluctuating (HR 1.24, 95% CI1.03-1.49) trajectories showed significantly higher MAFLD incidence. Random forest ranked MHR among top 5 predictors, and MR analyses supported a causal relationship.</p><p><strong>Conclusion: </strong>This multimodal study demonstrates that longitudinal MHR elevation precedes and predicts MAFLD development, implicating compounded inflammatory-lipid pathways. MHR trajectory anaylsis may enhance early risk stratification, particularly in metabolically compromised individuals.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12311-12322"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12430246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064801","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":"Programmed Cell Death of Chondrocytes, Synovial Cells, Osteoclasts, and Subchondral Bone Cells in Osteoarthritis.","authors":"Jiwei Huang, Longfei Wu, Yuhao Zhao, Haiyan Zhao","doi":"10.2147/JIR.S514309","DOIUrl":"10.2147/JIR.S514309","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Osteoarthritis (OA) is a common and debilitating chronic disease characterized by severe inflammation and progressive damage to adjacent tissues and cartilage. Traditional risk factors such as obesity, gender, and aging have long been recognized as contributing factors to osteoarthritis. Emerging evidence highlights that the dysregulation of programmed cell death (PCD) plays a crucial role in the pathogenesis and progression of this disease. Numerous studies have shown that various forms of programmed cell death, including ferroptosis, pyroptosis, autophagy, cuproptosis, and apoptosis, are closely associated with osteoarthritis. Ferroptosis is an iron-dependent cell death driven by lipid peroxidation, which is related to iron overload and oxidative stress in osteoarthritis, leading to chondrocyte dysfunction and cartilage degradation. Pyroptosis, an inflammatory cell death, is triggered by the activation of inflammasomes, promoting the release of pro-inflammatory cytokines, exacerbating joint inflammation, and accelerating disease progression. Autophagy, a cellular self-degradation process, has a dual role in osteoarthritis: it acts as a protective mechanism against stress in the early stage, but when autophagy is dysregulated, it promotes cartilage degeneration. Cuproptosis is a newly discovered copper-dependent cell death pathway, and since copper metabolism dysregulation affects the function of bone and cartilage cells, it is associated with osteoarthritis. Apoptosis is an actively regulated cell death process controlled by genes and is mediated by two main pathways. The extrinsic pathway is activated when death ligands bind to receptors, triggering the activation of caspase-8 and caspase-3; the intrinsic pathway is initiated by cellular stress factors such as DNA damage, leading to mitochondrial damage and the activation of caspase-9 and caspase-3. In osteoarthritis, inflammatory factors and oxidative stress activate these two pathways, accelerating the apoptosis of chondrocytes and disease progression.This review systematically elaborates on these different types of programmed cell death and their specific roles in the development and progression of osteoarthritis. It also delves into the latest research on the molecular mechanisms of these programmed cell death pathways in the context of osteoarthritis, clarifying how they interact with other cellular processes to drive disease development. In addition, the review summarizes the clinical applications of therapeutic methods targeting programmed cell death in osteoarthritis. Ingredients from traditional Chinese medicine and other drugs show potential in regulating ferroptosis, pyroptosis, autophagy, cuproptosis, and apoptosis to alleviate the symptoms of osteoarthritis. For example, &lt;i&gt;Icariin&lt;/i&gt; and &lt;i&gt;Myristicin&lt;/i&gt; can prevent ferroptosis, while &lt;i&gt;Matrine&lt;/i&gt; and metformin can reduce pyroptosis. Regarding cuproptosis, copper chelators and copper ion carriers are also under investig","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12323-12360"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064797","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":"SMP30 Attenuates Lens Epithelial Cells Pyroptosis of Cataract via the Downregulation of p-STAT3.","authors":"Yongshun Liang, Qingqiao Gan, Xin Zhong, Tian Lan, Yingqin Yang, Lixia Lin, Chengye Tang, Hao Liang","doi":"10.2147/JIR.S536127","DOIUrl":"10.2147/JIR.S536127","url":null,"abstract":"<p><strong>Background: </strong>To determine the effect of senescence marker protein 30 (SMP30) regulation on the levels of p-STAT3 in the pathophysiology of lens epithelial cells (LECs) pyroptosis in cataracts.</p><p><strong>Methods: </strong>Initially, cataracts were induced in rats using ultraviolet B (UVB) irradiation. Transmission electron microscopy was utilized to observe morphological changes in rat LECs, and RT-qPCR was utilized to quantify SMP30 and pyroptosis-related marker genes (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). Subsequently, SMP30-AAV2 vectors were injected into the vitreous cavity to overexpress SMP30 in rat lenses. Proteomic analysis identified differential proteins associated with pyroptosis post-SMP30 overexpression. Stable SMP30-overexpressing human LECs (SRA01/04 cells) were established via lentiviral transfection. Western blot, ELISA, and RT-qPCR were used to investigate the role of SMP30 in the pyroptosis of LECs treated with H₂O₂. Additionally, rescue experiments with p-STAT3 agonists and inhibitors elucidated SMP30's molecular mechanisms in H₂O₂-induced LECs pyroptosis.</p><p><strong>Results: </strong>After UVB irradiation, SMP30 expression significantly decreased in rat lens capsules, while pyroptosis-related marker gene expression markedly increased. Ten crucial pyroptosis-related proteins were identified by proteomic analysis following SMP30 overexpression, with STAT3 receiving the highest score. SMP30 overexpression during H₂O₂-induced pyroptosis in SRA01/04 cells significantly decreased the expression of pyroptosis-related markers (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). The p-STAT3 agonist Colivelin weakened the anti-pyroptotic effect of SMP30, while the p-STAT3 inhibitor Stattic enhanced the anti-pyroptotic effect of SMP30.</p><p><strong>Conclusion: </strong>The expression levels of SMP30 were downregulated in cataract cell pyroptosis. When overexpressed, SMP30 can reduce lens epithelial cell pyroptosis by downregulating the expression of p-STAT3. Thus, SMP30 demonstrates promising potential in preventing and treating cataracts.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12361-12377"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12428661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064866","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":"Development of Diagnostic and Predictive Models for COPD Based on Anoikis Resistance.","authors":"Wenmin Hu, Jingjing Sun, Mei Wang, Yaoyao Wang, Chaohui Mu, Xinjuan Yu, Peng Yuan, Wei Han, Yongchun Li, Qinghai Li","doi":"10.2147/JIR.S534626","DOIUrl":"10.2147/JIR.S534626","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) pathogenesis involves persistent airway inflammation and remodeling, yet the role of anoikis resistance remains poorly characterized. This study aimed to identify anoikis resistance-related hub genes and evaluate their clinical utility in COPD phenotyping and prognosis.</p><p><strong>Methods: </strong>Integrated bioinformatics analysis of the GSE11906 dataset identified anoikis resistance-related differentially expressed genes (DEGs). Functional enrichment, LASSO regression, and machine learning (RF, SVM, XGB, GLM) were employed to pinpoint core hub genes. Multi-level validation included external datasets (GSE19407), in vitro (CSE-stimulated 16HBE cells), in vivo (cigarette smoke-exposed mice), and clinical samples (PBMCs). Diagnostic and prognostic models were developed using logistic regression.</p><p><strong>Results: </strong>Five core hub genes (UCHL1, ME1, SLC2A1, BMP4, CRABP2) were identified, with ME1, SLC2A1, and BMP4 consistently upregulated in COPD across models and strongly correlated with emphysema index (negative, R = -0.41 to -0.45) and airway wall thickness (positive, R = 0.40-0.45). These genes exhibited significant associations with peribronchial immune cell infiltration. Diagnostic models for emphysema-predominant COPD (AUC = 0.860) and disease staging (AUC = 0.882), along with a prognostic model for hospitalization duration (AUC = 0.867), demonstrated robust clinical performance.</p><p><strong>Conclusion: </strong>ME1, SLC2A1, and BMP4 are pivotal anoikis resistance-related biomarkers in COPD, driving immune dysregulation and structural remodeling. The developed models enable precise phenotyping, severity stratification, and personalized prognosis prediction, advancing precision medicine strategies for COPD management.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12263-12278"},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040265","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":"Downregulation of IFIT3 Relieves the Inflammatory Response in Ulcerative Colitis via Selectively Regulating Macrophage M1 Polarization and the STAT1/2 Signaling Pathway.","authors":"Meiling Du, Yiran Tao, Ke Yang, Jin Liu, Xia Yang","doi":"10.2147/JIR.S542033","DOIUrl":"10.2147/JIR.S542033","url":null,"abstract":"<p><strong>Purpose: </strong>Ulcerative colitis (UC) is an inflammatory condition of the colon. Interferon-induced protein with tetratricopeptide repeat 3 (IFIT3), a member of the IFIT family, is known to be associated with antiviral immunity and cellular regulation. However, the functional and molecular mechanisms by which IFIT3 affects the occurrence and development of UC have not been reported.</p><p><strong>Patients and methods: </strong>Intestinal mucosa samples were collected from 22 UC patients and 20 healthy controls. After immunohistochemical staining and image analysis, the correlation between IFIT3 expression and clinical characteristics of UC patients was analyzed. Subsequently, we applied a dextran sulfate sodium (DSS)-induced colitis model in adeno-associated virus 9 -mediated IFIT3 silencing mice. Inflammatory cytokines and signal pathway molecules were examined. Moreover, THP-1 cells, lipopolysaccharide (LPS) and upadacitinib (UPA) were used in vitro experiments, and various assays were performed to evaluate IFIT3 expression, cellular responses, and signaling pathways.</p><p><strong>Results: </strong>First, our results demonstrated that IFIT3 was upregulated in colon tissues of UC patients and was positively correlated with the Mayo clinical score and fecal calprotectin levels. Second, knockdown of IFIT3 significantly attenuated the intestinal inflammatory response and reduced phosphorylated signal transducer and activator of transcription 1 and 2 (pSTAT1 and pSTAT2) protein levels in DSS-induced UC mice. Further mechanistic studies revealed that IFIT3 regulated LPS-induced M1 polarization in THP-1 macrophages by modulating the STAT1 signaling pathway. In addition, UPA exerted anti-inflammatory effects in vitro, to some extent, through the inhibition of IFIT3 expression.</p><p><strong>Conclusion: </strong>Our findings highlight the role of IFIT3 in inflammatory responses and macrophage polarization in colitis, suggesting that IFIT3 may be a promising target for UC treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12295-12309"},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064832","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":"Regulatory Mechanism and Drug Therapy of NLRP3 Inflammasome in Recurrent Pregnancy Loss: Research Status and Prospect.","authors":"Yonghan Cui, Yuqi Yang, Yuru Li, Yuwei Zhang, Dingren Niu, Xiaoling Feng","doi":"10.2147/JIR.S549048","DOIUrl":"10.2147/JIR.S549048","url":null,"abstract":"<p><p>Recurrent pregnancy loss (RPL) is a distressing reproductive system disease with complex underlying causes and difficult treatment, making it a common fertility challenge for women of childbearing age. In recent years, the role of inflammasomes in RPL has gradually been recognized. NOD-like receptor family pyrin domain-containing 3 (NLRP3) is a key component of the innate immune system and a central regulator of inflammatory signaling. Accumulating evidence links NLRP3 inflammasome activation to female reproduction. During pregnancy, the assembly and activation of the NLRP3 inflammasome generate pro-inflammatory cytokines and pyroptosis-associated factors that engage in extensive cross-talk with other inflammatory pathways, thereby contributing to RPL through diverse mechanisms, including inflammatory cascades, endometrial receptivity, immune cell differentiation and polarization, pyroptotic cell death, autophagy, and intestinal barrier permeability. A detailed understanding of these intricate interactions may unveil novel therapeutic targets and strategies to mitigate the physiological and psychological burden of RPL on affected couples. However, currently there are still limited RPL therapeutic drugs targeting NLRP3. Developing drugs that precisely target and regulate NLRP3 is expected to promote the development of RPL therapy research. This comprehensive review investigates the complex relationship between NLRP3 inflammasome and RPL, highlighting the central role of inflammation in disease progression. It also summarizes potential drugs targeting NLRP3 inflammasome for the treatment of RPL, providing theoretical basis for potential clinical therapeutic targets.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12279-12294"},"PeriodicalIF":4.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040281","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":"Therapeutic Potential of Acupuncture in Knee Osteoarthritis: Clinical Efficacy and Mechanistic Insights.","authors":"Kaifang Yao, Md Forhad Shamim, Jiaqi Xia, Tingting Tingting Liu, Yi Guo, Xiaowei Lin","doi":"10.2147/JIR.S526890","DOIUrl":"10.2147/JIR.S526890","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a prevalent degenerative joint disorder that significantly compromises joint function due to the progressive degradation of cartilage and persistent inflammation. Acupuncture is an effective technique that has been employed in Traditional Chinese Medicine to treat KOA. This review aims to summarize 21 randomized controlled trials (RCTs) and mechanistic research to investigate acupuncture's clinical efficacy and biological mechanisms in KOA. The literature was sourced from various databases, including PubMed, CNKI, and Google Scholar. Clinical data revealed that acupuncture monotherapy significantly reduces pain intensity (Visual Analogue Scale reductions: 32-54%) and enhances functional capacity (WOMAC score improvements: 25-40%). Furthermore, the combination of acupuncture with moxibustion or electroacupuncture induced synergistic improvements. Mechanistically, acupuncture modulates KOA pathophysiology by suppressing NF-κB-mediated pro-inflammatory cytokines, inhibiting chondrocyte apoptosis (caspase-3 downregulation) while activating autophagy (LC3-II/Beclin-1 upregulation), rebalancing cartilage metabolism by increasing aggrecan/COL2A1 synthesis and MMP-13 inhibition, as well as by attenuating pain transmission through μ-opioid receptor activation and central descending inhibition. These multimodal interventions position acupuncture as a dual-target treatment, mitigating symptoms while inhibiting structural degradation. However, despite promising evidence, further research is warranted for protocol standardization and long-term outcome validation. This review highlights acupuncture's scientific legitimacy as a non-pharmacological approach for the integrated management of KOA, combining traditional methods with modern mechanistic insights.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12169-12190"},"PeriodicalIF":4.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040235","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":"Exploring the Intervention Mechanism of Effective-Component Combination of Bufei Yishen Formula III for Airway Epithelial Barrier Injury: A miRNA-mRNA Regulatory Network Analysis.","authors":"Chunlei Liu, Changyuan Yue, Xiaoxiang Xing, Lidong Huang, Yanxin Wei, Peng Zhao, Jiansheng Li, Qingzhou Guan","doi":"10.2147/JIR.S529587","DOIUrl":"10.2147/JIR.S529587","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the mechanism by which the effective-component combination of Bufei Yishen formula III (ECC-BYF III) ameliorates airway epithelial barrier injury in chronic obstructive pulmonary disease (COPD) through miRNA-mRNA regulatory networks.</p><p><strong>Methods: </strong>Differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified using the edgeR algorithm. The target genes of DEmiRNAs were predicted using four online databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis based on the hypergeometric distribution model was performed for DEmRNAs and the predicted target genes, respectively. DEmiRNAs and their corresponding target genes that were regulated by ECC-BYF III were subsequently identified. The reliability of these miRNAs and target genes was validated using independent datasets, qRT-PCR in human bronchial airway epithelial cells (BEAS-2B), COPD rat models, and molecular docking.</p><p><strong>Results: </strong>Compared with the control group, 2997 DEmRNAs and 4 DEmiRNAs were identified in the model group (edgeR, <i>P</i><0.05). A total of 2430 target genes of the DEmiRNAs were predicted, and the miRNA-mRNA regulatory network was constructed. Pathway enrichment analysis revealed that DEmRNAs were enriched in 96 pathways and target genes in 112 pathways, with 53 overlapping pathways (<i>P</i><0.05). ECC-BYF III treatment reversed the expression of 13 miRNA-mRNA pairs. Further screening and validation in COPD rat models and BEAS-2B cells identified two miRNAs and five regulated hub genes (ESM1, RNF44, BCL2L1, ADAM19, and SMYD5). The reliability of these hub genes was further confirmed by independent datasets (GSE173896 and GSE11906) and molecular docking.</p><p><strong>Conclusion: </strong>ECC-BYF III may alleviate airway epithelial barrier injury in COPD by regulating the hsa-miR-3685-ESM1 and hsa-miR-3936-RNF44/BCL2L1/ADAM19/SMYD5 networks.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12145-12167"},"PeriodicalIF":4.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040278","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}