Journal of Inflammation Research最新文献

{"title":"Gut-Spinal Cord Axis in Spinal Cord Injury: Bidirectional Inflammatory Mechanisms and Microbiota-Targeted Therapeutic Strategies.","authors":"Jinwang Dong, Tao Xie, Cunhu Shi, Gaoqi Feng, Hengheng Zhang, Zhengwei Xu, Liang Dong","doi":"10.2147/JIR.S543912","DOIUrl":"10.2147/JIR.S543912","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a complex neurological disorder characterized not only by localized neuroinflammation but also by systemic immune dysregulation and multiorgan dysfunction. Emerging evidence has identified the gut microbiota as a critical extrinsic regulator of neural homeostasis, giving rise to the concept of the \"gut-spinal cord axis\". This review systematically examines the dynamic and bidirectional alterations in the gut microbial composition following SCI, with a particular emphasis on the role of microbiota-derived metabolites in the gut-spinal cord axis. These metabolites are recognized as key mediators that shape the spinal inflammatory milieu by modulating specific signaling pathways. In addition, the mechanistic basis of the gut-spinal cord axis is further dissected through neural, immune, and metabolic regulatory frameworks, highlighting how gut dysbiosis following SCI contributes to spinal inflammation via the modulation of vagal nerve signaling, immune cell polarization, and metabolic homeostasis. Moreover, the translational potential of microbiota-targeted interventions-such as probiotics and fecal microbiota transplantation (FMT)-is evaluated in terms of their ability to suppress inflammatory amplification and restore the disrupted bidirectional gut-spinal cord feedback loop. By integrating multiomics approaches and adopting a spatiotemporal perspective, this review underscores the importance of cross-system therapeutic strategies in SCI, aiming to provide a theoretical foundation and practical guidance for future precision interventions and translational research.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12549-12573"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080894","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 Bidirectional Role of Obesity and Aging in the Pathogenesis of Osteoarthritis: Molecular Mechanisms, Epigenetic Insights, and Therapeutic Implications.","authors":"Chuang Lin, Junxing Yang, Hang Su, Xinguo Zhang, Bo Wang","doi":"10.2147/JIR.S514521","DOIUrl":"10.2147/JIR.S514521","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a major global contributor to pain, disability, and socioeconomic burden. With the increasing prevalence of obesity and an aging population, the incidence of OA continues to rise. This review explores the bidirectional relationship between obesity and aging in the pathogenesis of OA, focusing on the underlying molecular mechanisms. Obesity contributes to aging by inducing oxidative stress, chronic inflammation, and metabolic dysregulation, thereby promoting OA development and progression. Conversely, the accumulation of senescent cells with age exacerbates obesity-induced inflammation and metabolic dysfunction by secreting pro-inflammatory cytokines and bioactive molecules. Epigenetic changes, including DNA methylation, histone modifications, and the regulation of non-coding RNAs, play pivotal roles in modulating these interactions, further influencing OA progression. The review also discusses current and emerging therapeutic strategies targeting the obesity-aging-OA axis, highlighting the potential of epigenetic interventions and novel anti-inflammatory treatments. A comprehensive understanding of the molecular interplay between obesity and aging in OA is essential for developing more effective prevention and treatment strategies. Future research should prioritize the in-depth exploration of epigenetic mechanisms, coupled with technological innovation, standardized education and training, quality control, and multidisciplinary collaboration. Targeted strategies and interventions are essential to effectively prevent and manage obesity- and OA-related diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12637-12676"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080953","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":"Viral Triggers Exposed: A Systematic Review of Virus-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.","authors":"Ulfa Fetriani, Dewi Zakiawati","doi":"10.2147/JIR.S546186","DOIUrl":"10.2147/JIR.S546186","url":null,"abstract":"<p><strong>Aim: </strong>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin conditions characterized by widespread epidermal necrolysis and mucous membrane involvement. SJS affects less than 10% of the body surface area, while TEN involves over 30%, with cases between 10% and 30% classified as SJS/TEN overlap. Drug hypersensitivity reactions, especially to antibiotics, anticonvulsants, and non-steroidal anti-inflammatory medications, are the most common and well-established causes of SJS/TEN. In addition, infections, including viral ones like herpes simplex virus (HSV), influenza virus, varicella-zoster virus, and human immunodeficiency virus (HIV), have also been implicated as potential inducers, complicating management and requiring careful clinical vigilance.</p><p><strong>Purpose: </strong>This review aims to investigate and compile information on reported cases of SJS/TEN potentially linked to virus infections.</p><p><strong>Methods: </strong>Literature from PubMed, NCBI, ScienceDirect, and Cochrane Library databases was searched. The inclusion criteria were studies reporting details of patients diagnosed with SJS, TEN, or SJS/TEN overlap, potentially induced by viral infections. Cases were included if the viral infection occurred within one week before the rash onset, emphasizing the association between these infections and severe skin reactions.</p><p><strong>Results: </strong>Ten studies were included in this systematic review, most of which demonstrated fair to good methodological quality. The review encompassed cases of virus-induced SJS/TEN, including herpes virus infection, influenza virus infection, varicella-zoster virus, HIV infection, COVID-19, and coxsackie infection, each with distinct manifestations.</p><p><strong>Conclusion: </strong>The evidence strongly suggests that viral infections contribute to the development of SJS/TEN, yet the precise mechanisms remain unclear and warrant further research. Awareness of this risk is crucial, particularly in regions experiencing outbreaks of these viruses.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12575-12588"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080878","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 Inflammatory-Related Factors Associated with Postoperative Length of Hospital Stay in Elderly Patients Undergoing Gastrointestinal Tumor Surgery Using Machine Learning.","authors":"Jing Liu, Yubang Hu, Xiaoxuan Zhan, Huanwei Wang, Cai Li","doi":"10.2147/JIR.S542616","DOIUrl":"10.2147/JIR.S542616","url":null,"abstract":"<p><strong>Background: </strong>The influencing factors of postoperative recovery in elderly patients undergoing gastrointestinal tumor surgery are complex, and inflammatory responses have been confirmed to play a critical role. However, the specific impact of inflammatory cells on postoperative length of hospital stay (LOS) in elderly patients following general anesthesia for gastrointestinal surgery remains unclear.</p><p><strong>Methods: </strong>This study collected perioperative data from elderly patients who underwent gastrointestinal tumor surgery at a tertiary hospital between 2019 and 2023. By analyzing the relationship between perioperative factors and postoperative LOS, we first used the LASSO algorithm for variable selection and then employed XGBoost modeling to identify factors associated with rapid (LOS < 7 days) and delayed (LOS > 12 days) discharge. We further explored how inflammatory cells affect postoperative recovery in elderly patients, with results visualized using SHAP (SHapley Additive exPlanations) plots.</p><p><strong>Results: </strong>A total of 300 elderly patients who underwent gastrointestinal tumor resection were included, with 58.7% male and a mean age of 72 ± 6.4 years. Key factors associated with rapid discharge included operative time, age, blood loss, total intraoperative fluid input, urine output, preoperative neutrophil percentage, hemoglobin, and preoperative creatinine. Specifically, a preoperative neutrophil percentage in the 60%-70% range was linked to faster discharge. For delayed discharge, significant factors included age, operative time, preoperative creatinine, preoperative hemoglobin, preoperative neutrophil percentage, intraoperative urine output, the difference in neutrophil counts between pre- and postoperative periods, total intraoperative fluid input, and blood loss. Patients with preoperative neutrophil percentages of 70%-80% and neutrophil count differences of 5%-25% were more likely to experience delayed discharge.</p><p><strong>Conclusion: </strong>In elderly patients undergoing gastrointestinal tumor resection, preoperative neutrophil percentage and the change in neutrophil percentages from pre- to postoperative periods significantly influence postoperative LOS.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12589-12597"},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080900","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 Lipid-Oxidative Stress Axis: Novel Therapeutic Targets for Podocytopathy.","authors":"Yingxi Liu, Manshu Zou, Yuhong Wang","doi":"10.2147/JIR.S530737","DOIUrl":"10.2147/JIR.S530737","url":null,"abstract":"<p><p>Podocytes, as terminally differentiated cells within the glomerulus, play a decisive role in maintaining the molecular selectivity of the glomerular filtration barrier (GFB) through structural integrity and functional homeostasis. Podocyte injury not only directly compromises GFB integrity but also serves as a central pathological mechanism underlying the progression of proteinuric nephropathy. Evidence from studies highlights an intricate link between lipid metabolism dysregulation and podocyte dysfunction: Renal ectopic lipid accumulation (ELA) disrupts intracellular homeostasis via lipotoxic effects, inducing mitochondrial oxidative stress, cytoskeletal remodeling, and inflammatory cascades. Concurrently, excessive reactive oxygen species (ROS) generation coupled with compromised antioxidant defense mechanisms establishes a self-perpetuating cycle of redox imbalance. This bidirectional crosstalk within the lipid-oxidative stress axis triggers irreversible pathological alterations. This review summarizes the effects of abnormal signals during lipid synthesis, breakdown, and metabolism on podocytes, as well as the interaction between mitochondria and podocyte dysfunction through signaling mechanisms in lipid metabolism disorders. We also sorted out the key molecular pathways involved in this axis, and the regulation of key nodes of lipid metabolism (SREBP pathway, HMGCR pathway), improvement of mitochondrial function (mitochondrial dynamics and energy metabolism), and activation of antioxidant defenses (AMPK pathway) are highly promising therapeutic targets for intervening in podocyte damage and blocking the progression of the disease.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12505-12532"},"PeriodicalIF":4.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075481","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":"Angiotensin-(1-7) Inhibits Angiogenesis and Alleviates Joint Damage in CIA Mice via the Hippo-YAP Pathway.","authors":"Shan Zhang, Min Sheng, Dan Yu, Kechen Qian, Yichen Zhang, Wenhan Huang, Feifeng Ren, Lin Tang","doi":"10.2147/JIR.S534282","DOIUrl":"10.2147/JIR.S534282","url":null,"abstract":"<p><strong>Purpose: </strong>Angiotensin-(1-7) [Ang-(1-7)], a bioactive peptide of the renin‒angiotensin system, exerts potent anti-inflammatory, antifibrotic and metabolic regulatory effects. Ang-(1-7) inhibits synovial inflammation and bone destruction in collagen-induced arthritis (CIA) model mice, but its role in rheumatoid arthritis (RA) angiogenesis remains unknown. This study aimed to investigate the effect of Ang-(1-7) on synovial angiogenesis in CIA mice.</p><p><strong>Methods: </strong>Arthritis scores and histopathology were used to assess the anti-inflammatory and joint damage-alleviating effects of Ang-(1-7) in CIA mice. Immunohistochemistry and immunofluorescence were used to detect vascular density in the synovium of CIA mice. The proliferation, migration, and tube formation abilities and the expression of angiogenic mediators of tumor necrosis factor-alpha (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) were examined to assess Ang-(1-7) antiangiogenic activity. Immunofluorescence and Western blotting were used to analyze the protein levels, phosphorylation, and nuclear translocation of large tumor suppressor kinase 1 (LATS1) and Yes-associated protein (YAP) in CIA mice and TNF-α-induced HUVECs.</p><p><strong>Results: </strong>Ang-(1-7) treatment significantly reduced systemic inflammation in CIA mice, inhibited angiogenesis in the synovium, and attenuated synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction. Ang-(1-7) also inhibited TNF-α-induced HUVEC proliferation, migration, and tube formation. Mechanistic investigations revealed that Ang-(1-7) exerted its therapeutic effects through modulation of the Hippo-YAP pathway. Ang-(1-7) significantly downregulated LATS1 and YAP expression while restoring their phosphorylation status. Furthermore, Ang-(1-7) inhibited YAP nuclear translocation, subsequently suppressing downstream targets, including hypoxia-inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2). The effects of Ang-(1-7) were partially blocked by the Mas receptor antagonist A779.</p><p><strong>Conclusion: </strong>Ang-(1-7) acts on the Mas receptor to regulate Hippo-YAP signaling, inhibit YAP activation, and suppress the production of HIF-1, VEGF and VEGFR2. This leads to the suppression of TNF-α-stimulated HUVEC activity, thereby attenuating synovial angiogenesis, inflammation, and joint damage in CIA mice.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12401-12419"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069736","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":"Upadacitinib Attenuates Lipopolysaccharide- and Cecal Ligation and Puncture-Induced Inflammatory Responses by Inhibiting NF-κB and Its Downstream Cytokines.","authors":"Qi Yao, Xueting Yang, Hongli Yan, Yang Wang, Yanlin Ma, Ning Xu","doi":"10.2147/JIR.S535747","DOIUrl":"10.2147/JIR.S535747","url":null,"abstract":"<p><strong>Background: </strong>Upadacitinib (UPA) is a selective tyrosine kinase 1 (JAK-1) inhibitor, which has been applied to treat atopic dermatitis, psoriatic arthritis, and ulcerative colitis in clinic. Whether it can treat sepsis remains unclear. Here, we investigate the effect of UPA on lipopolysaccharide (LPS)- and cecal ligation and puncture (CLP)-induced inflammatory responses in vitro and in vivo.</p><p><strong>Methods: </strong>In vitro, LPS-treated RAW264.7 cell line, LPS-treated TLR4 knock-out (TLR4^-/-) RAW264.7 cell line, and LPS-treated NLRP3 knock-out (NLRP3^-/-) RAW264.7 cell line were used. In vivo, CLP-treated mice and CLP-treated TLR4^-/- mice were used. Proteomics was used to screen inflammation-related differential proteins in RAW264.7 cells after treatments. After that, Western blotting was used to investigate the potential mechanism.</p><p><strong>Results: </strong>In vitro, UPA significantly inhibited TLR4/NF-κB and JAK/STAT pathway in the LPS-treated RAW264.7 cells. In addition, UPA reduced protein expressions of NF-κB and its downstream inflammatory cytokines such as TNF-α, IL-1β in the LPS-treated TLR4^-/- RAW264.7 cells. In vivo, UPA markedly protected the sepsis mice, decreased intestinal injuries, reduced bacterial load, and downregulated the TLR4/NF-κB and JAK/STAT pathways-related proteins in macrophages isolated from peritoneal lavage fluids (PLFs) of the sepsis mice. In fact, UPA still exerted the protective effect in the CLP-treated TLR4^-/- mice. The proteomics revealed that NOD-like receptor (NLR) signaling was one of the most significantly affected pathways between the LPS-treated and UPA-treated. Although UPA significantly reduced NLRP3 and IL-1β protein expressions in the LPS-treated RAW264.7 cells, its anti-inflammatory effect was not significantly abolished in the LPS-treated NLRP3^-/- RAW264.7 cells.</p><p><strong>Conclusion: </strong>Taken together, UPA inhibits the LPS- and CLP-induced inflammatory responses in vitro and in vivo, which is associated with the inhibition of NF-κB and its downstream cytokines.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12533-12548"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069744","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":"Quercetin-Loaded Nanoparticles: A Promising Therapeutic Strategy for Inflammatory Bowel Disease.","authors":"Wenpeng Wang, Mingrui Li, Ying Liu, Benno Weigmann","doi":"10.2147/JIR.S545203","DOIUrl":"10.2147/JIR.S545203","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to evaluate the characteristics and therapeutic efficacy of quercetin-loaded nanoparticles (NPs) using poly lactic-co-glycolic acid (PLGA) and Eudragit S100 (ES100) as carriers in the treatment of inflammatory bowel disease (IBD).</p><p><strong>Materials and methods: </strong>Quercetin-loaded NPs were prepared using PLGA (QU-PLGA) and a combination of PLGA and ES100 (QU-PE). The mean particle sizes, encapsulation efficiencies, and stability of quercetin in aqueous solutions were assessed. Drug release profiles were evaluated under different pH conditions. In vitro studies involved cell endocytosis and cytotoxicity assays using Caco-2 and SW480 cells. In vivo efficacy was tested in dextran sulfate sodium (DSS) and oxazolone (OXA) induced acute colitis models in mice, with assessments including weight retention, colonic length, Murine Endoscopic Index of Colitis Severity (MEICS), histological scores, and inflammatory markers.</p><p><strong>Results: </strong>Quercetin-loaded NPs (QU-PLGA: 160.4 ± 3.68 nm; QU-PE: 161.0 ± 2.30 nm) exhibited significantly smaller particle sizes compared to free quercetin (QU-Free: 2239 ± 404 nm) and high encapsulation efficiencies (87-90%). QU-PE showed pH-dependent release with improved stability in aqueous solutions. Quercetin-loaded NPs demonstrated enhanced cell membrane penetration and were non-toxic at tested concentrations. In the DSS and OXA colitis models, quercetin-loaded NPs significantly reduced disease severity, as evidenced by improved weight retention, longer colonic length, reduced MEICS and histological scores, decreased pro-inflammatory cytokines, and higher E-Cadherin expression compared to untreated groups. Notably, QU-PE demonstrated consistent anti-inflammatory effects across both models, with particularly pronounced efficacy in OXA-induced colitis, while QU-PLGA showed relatively superior therapeutic performance in the DSS model.</p><p><strong>Conclusion: </strong>Quercetin-loaded NPs enhance the stability, bioavailability, and therapeutic efficacy of quercetin in IBD, offering a promising therapeutic strategy with superior physiological relevance for colitis treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12447-12461"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069750","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":"SCIN: A Key Driver in Chronic Atrophic Gastritis-Gastric Cancer Cascade with Implications for Immunity and Prognosis.","authors":"Kairui Wu, Yu Ye, Bei Pei, Biao Song, Tingting Li, Qi Yang, Yueping Jin, Xuejun Li","doi":"10.2147/JIR.S545499","DOIUrl":"10.2147/JIR.S545499","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a major global health burden, and chronic atrophic gastritis (CAG), a key precancerous lesion in the Correa cascade, is critical in its pathogenesis. As a Ca²⁺-dependent actin-regulating protein, scinderin (SCIN) has been implicated in tumor progression across multiple malignancies, including gastric cancer. This study investigated SCIN expression dynamics during CAG-to-GC progression, its association with the tumor immune microenvironment (TIME) and clinical prognosis, and validated its role via integrated bioinformatics and experiments.</p><p><strong>Methods: </strong>Transcriptomic data from TCGA and GEO were analyzed using R. WGCNA and ceRNA networks identified SCIN as the core RNA and its interacting miRNAs/lncRNAs. GSVA, GSEA, immune infiltration, and checkpoint analyses explored SCIN's immunological relevance. Prognostic value was assessed via Cox models and ROC curves. SCIN expression was validated in 28 human gastric tissues by RT-qPCR and Western blotting. Functional assays (CCK-8, Transwell, flow cytometry) investigated its role in GC cells.</p><p><strong>Results: </strong>SCIN expression significantly increased along normal mucosa→CAG→GC, with high diagnostic performance (AUC). Elevated SCIN correlated with poor survival and served as an independent prognostic factor. It was involved in immune-related pathways, modulated the TIME, and correlated with immune checkpoint markers. SCIN knockdown inhibited GC cell migration, enhanced apoptosis, and altered cell cycle.</p><p><strong>Conclusion: </strong>This study is the first to identify SCIN as a key molecular driver in the CAG-to-GC transition. SCIN represents a robust prognostic biomarker and a potential target for immunotherapeutic intervention in GC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12485-12503"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069692","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":"Urolithin-C Suppresses Inflammation by Blocking NF-κB Signaling Pathway in LPS-Induced RAW 264.7 Macrophages.","authors":"Vani Karadi Manjappa, Manjula Mavathuru Venkatappa, Deepadarshan Urs, Suliphuldevara Mathada Basavarajaiah, Shivakumar Venkataramaiah, Sanjana Bai Shivramsingh Mahendranathsingh, Sushma Mohan, Hunase Rajaiah Pushpavathi, Dharmappa Kattepura Krishnappa, Devaraja Sannaningaiah","doi":"10.2147/JIR.S539273","DOIUrl":"10.2147/JIR.S539273","url":null,"abstract":"<p><strong>Purpose: </strong>In the current study, the evaluation of anti-inflammatory <i>(in</i> <i>vitro</i>) activity of chemically synthesized Urolithin-C was examined.</p><p><strong>Methods: </strong>The synthesis of Urolithin-C (3,8,9-trihydroxy-6H-benzo[c]chromen-6-one) was carried out by chemical method and it was characterized using various techniques. The anti-inflammatory efficacy of synthesized Urolithin-C was studied by membrane stabilization, protein denaturation and protease inhibition assays. In addition, MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide) assay was employed to evaluate the cytotoxic effect of Urolithin-C. The anti-inflammatory property of Urolithin-C was further examined using LPS (Lipopolysaccharide) induced RAW 264.7 (Mouse macrophage) cells. Furthermore, the anti-inflammatory properties of Urolithin-C was studied by quantifying pro/anti-inflammatory cytokines using ELISA (enzyme-linked immunosorbent assay). The mechanism of action of Urolithin-C on NF-κB (Nuclear Factor-kappa B) translocation was studied using CLSM (confocal laser scanning microscopy). While gene expression pattern was analyzed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction).</p><p><strong>Results: </strong>In comparison to the positive control aspirin, Urolithin-C showed a strong anti-inflammatory effect by preventing lysosomal degradation, protein denaturation and inhibition of protease. Furthermore, at the higher dose (200 µg/mL), Urolithin-C was found to be toxic to the mouse macrophages; however, at lower concentration (25 µg/mL) it did not cause toxicity to the said. Thus, 25 µg/mL of Urolithin-C was used to assess the anti-inflammatory activity. Interestingly, Urolithin-C efficiently reduced the expression of pro-inflammatory inducible enzyme (Cox-2), cytokines (IL-2, IL-6, and TNF-alpha) and increased the anti-inflammatory cytokine (TGF-beta1), compared to positive control diclofenac (DFC). Urolithin-C effectively abrogated the NF-κB p65 phosphorylation and its translocation to the nucleus as well. Most importantly, Urolithin-C efficiently suppressed the expression of pro-inflammatory genes and elevated the expression of anti-inflammatory gene.</p><p><strong>Conclusion: </strong>Urolithin-C exhibited anti-inflammatory properties by regulating the expression of pro-inflammatory inducible enzyme, cytokines and the translocation of NF-κB p65 to the nucleus.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"12463-12483"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064789","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}