Journal of Inflammation Research最新文献

{"title":"Succinate Facilitates CD4⁺ T Cell Infiltration and CCL1 Production to Promote Myofibroblast Activation and Renal Fibrosis in UUO Mice.","authors":"Yuandong Tao, Wei Zhang, Dehong Liu, Hualin Cao, Xiaoyu Yi, Xiangling Deng, Pin Li, Xiaoli Shen, Huixia Zhou","doi":"10.2147/JIR.S510637","DOIUrl":"10.2147/JIR.S510637","url":null,"abstract":"<p><strong>Aim: </strong>Obstructive nephropathy is a leading cause of kidney injury and fibrosis, which is always associated with metabolic aberrations and chronic inflammation. Succinate is an important intermediate metabolite involved in inflammatory responses and various diseases. However, the precise pathogenic mechanisms of succinate in obstructive nephropathy remain to be elucidated.</p><p><strong>Methods: </strong>Succinate was supplemented in the drinking water to study its impact on the pathogenesis of obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in mice. Kidney fibrosis, injury, inflammatory cytokines, and infiltrated immune cells were analyzed. Transcriptome analysis and in vitro studies were performed to study the cellular and molecular mechanisms by which succinate regulates CD4⁺ T cells and renal fibrosis.</p><p><strong>Results: </strong>Kidney proteomics revealed that the tricarboxylic acid (TCA) cycle and mitochondrial dysfunction were the hallmarks of obstructive nephropathy. Succinate was significantly accumulated in the obstructed kidneys. Succinate supplementation promoted UUO-induced renal fibrosis, injury, and inflammation. Moreover, succinate facilitated renal infiltration of CD4⁺ T cells by upregulating the T-cell chemokines CXCL9 and CXCL10. Transcriptome analysis suggested that succinate promoted CD4⁺ T cell activation and induced the production of CCL1, which mediated the transition of fibroblasts to myofibroblasts through the ERK signaling pathway. Recombinant CCL1 treatment promoted UUO-induced renal fibrosis and inflammation.</p><p><strong>Conclusion: </strong>Our study uncovers the important role of succinate in mediating T-cell response that orchestrates the pathogenesis of obstructive nephropathy. Targeting succinate accumulation may be a therapeutic strategy for the treatment of obstructive nephropathy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7827-7840"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333272","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":"Dysbiosis of Gut Microbiota in Ankylosing Spondylitis Patients.","authors":"Lianjun Yang, Kun Wang, Bin Liu, Tao Chen, Tao Ma, Zhifei Cui, Dawei Zhang, Shiyanjin Zhang, Xiang Liu, Jun Shen, Hai Lu","doi":"10.2147/JIR.S517979","DOIUrl":"10.2147/JIR.S517979","url":null,"abstract":"<p><strong>Purpose: </strong>Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with genetic, immune, and microbial factors. The role of gut microbiota in the pathogenesis of AS is increasingly recognized, with studies suggesting that intestinal dysfunction may trigger systemic inflammation. This study aimed to investigate the gut microbiota profiles of AS patients from Southern China and explore the relationship between gut microbiota and the occurrence and development of AS.</p><p><strong>Patients and methods: </strong>We enrolled 30 AS patients and 25 healthy controls from the Fifth Affiliated Hospital of Sun Yat-sen University. Fecal samples were collected, and DNA was extracted for 16S rDNA sequencing to analyze the V3-V4 variable regions. Bioinformatic processing and statistical analysis were performed to assess the microbial community structure, diversity, and function.</p><p><strong>Results: </strong>The study revealed significant differences in gut microbiota composition between AS patients and healthy controls. AS patients exhibited a decrease in beneficial bacteria such as Firmicutes and Actinobacteria and an increase in harmful bacteria like Proteobacteria and Enterobacteriaceae. The functional prediction of gut microbiota indicated significant metabolic pathway alterations, particularly in energy metabolism, degradation metabolism, and nucleotide metabolism, which may be linked to the pathophysiology of AS.</p><p><strong>Conclusion: </strong>This study demonstrates that the gut microbiota of Han Chinese AS patients in Guangdong Province is characterized by a decrease in beneficial bacterial communities and an increase in harmful ones, potentially contributing to AS progression through intestinal barrier disruption and intensified inflammatory responses. These findings provide a theoretical basis for developing new intervention strategies targeting the gut microbiota.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7841-7854"},"PeriodicalIF":4.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333271","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 Pattern Recognition Receptors in Epigenetic and Metabolic Reprogramming: Insights into Trained Immunity.","authors":"Yanjie Li, Mingzhu Chen, Junxiong Li, Jiangtian Hu","doi":"10.2147/JIR.S513325","DOIUrl":"10.2147/JIR.S513325","url":null,"abstract":"<p><p>Pattern recognition receptors (PRRs) function as pivotal components of the innate immune system by orchestrating trained immunity through dynamic epigenetic and metabolic reprogramming. Recent discoveries demonstrate that PRRs not only detect pathogens but also actively regulate immune cell metabolism and transcriptional landscapes, thereby potentiating the speed and magnitude of defensive responses upon secondary challenges. These functional adaptations are coordinated through evolutionarily conserved signaling cascades that establish persistent immunological modifications at cellular and systemic levels. Nevertheless, despite substantial advances in characterizing PRR-driven immune activation, the molecular mechanisms governing their role in innate immune memory formation remain incompletely elucidated. This review systematically explores emerging paradigms of PRR-mediated epigenetic remodeling and metabolic rewiring, with particular emphasis on their mechanistic integration into trained immunity. We critically assess current evidence, identify unresolved questions regarding signal transduction specificity and memory maintenance, and propose novel methodological approaches to decipher the multilayered regulatory networks of innate immune adaptation. By elucidating these processes, our analysis establishes a conceptual framework for developing immunomodulatory therapies and leveraging trained immunity in precision medicine applications.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7795-7811"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325981","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":"Feedback Regulation of sPLA2-COX/5-LOX-Ca2+ in Seminal Plasma and Its Impact on Sperm Quality Parameters.","authors":"Yongjie Liu, Liang Dai, Fan Zhang, Yang Liu, Xu Li, Wenzhi Ma","doi":"10.2147/JIR.S523172","DOIUrl":"10.2147/JIR.S523172","url":null,"abstract":"<p><strong>Background: </strong>Male reproductive health is of growing concern. Sperm quality declines due to multiple factors. The role of AA metabolic network in sperm quality is unclear, and AA/COX's protection under heat stress needs study.</p><p><strong>Aim: </strong>This study aimed to investigate the relationship between seminal plasma arachidonic acid (AA) metabolic network markers and sperm quality, as well as explore the protective effects of AA and cyclooxygenase (COX) on sperm under heat stress.</p><p><strong>Methods: </strong>We analyzed 164 seminal plasma samples from 164 male infertility patients, categorized by sperm concentration and motility (PR < 32% vs PR ≥ 32%). A heat-stressed weak spermatogenesis model (37-42°C) was established, and AA/COX were added in vitro to assess their impact on sperm quality.</p><p><strong>Results: </strong>Significant correlations were found between AA pathway markers (PL, sPLA2, AA, COX1/2, PGE1, PGF2α, 5-LOX, LTB4) and sperm parameters (motility, acrosome reaction, mitochondrial function, DNA fragmentation). A predictive model combining PL, AA, and COX1 effectively assessed sperm quality. In vitro, 100 pg AA ± 300 pg COX1 protected sperm at 42°C by upregulating COX2, PGE1, and PGF2α while reducing LOX/LTB4 and modulating Ca²⁺ levels, improving acrosome reactivity and reducing oxidative stress.</p><p><strong>Conclusion: </strong>Seminal plasma AA metabolism strongly influences sperm quality, likely via sPLA2-COX/5-LOX-Ca²⁺ feedback mechanisms. The PL-AA-COX1 model may serve as a sperm quality predictor, and AA/COX1 supplementation could protect sperm under heat stress.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7381-7400"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325976","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 Autophagy in the Regulation of Bidirectional Relationships in Diabetic Periodontitis.","authors":"Na Li, Qi Chen, Yi Feng, Yin Wang","doi":"10.2147/JIR.S533791","DOIUrl":"10.2147/JIR.S533791","url":null,"abstract":"<p><p>A bidirectional relationship exists between diabetes and periodontitis. For individuals with diabetes, hyperglycemia can exacerbate periodontal tissue destruction by triggering inflammatory responses, enhancing oxidative stress, and promoting alveolar bone resorption. Meanwhile, as a chronic inflammatory disease, periodontitis involves periodontal pathogens and their secreted virulence factors, which can elicit systemic inflammatory responses. Consequently, this intensifies insulin resistance and elevates blood glucose levels, establishing a vicious cycle. Despite extensive research on the association between diabetes and periodontitis, the precise mechanisms underlying this connection remain a topic of ongoing debate. Autophagy, a crucial defensive mechanism responsible for maintaining cellular homeostasis, plays a vital role in this relationship. Emerging evidence indicates that autophagy influences inflammation in periodontal tissue and blood glucose levels by regulating pathogen clearance, modulating inflammatory and immune responses, maintaining bone metabolism, and fine-tuning autophagic activity. As such, targeting modulation of autophagy represents a promising therapeutic strategy for managing diabetic periodontitis. In this paper, we will provide a review of the mechanisms of autophagy in the bidirectional relationship between diabetes and periodontitis. Elucidating these mechanisms will enhance a more profound comprehension of the intricate relationship between diabetes and periodontitis, provide novel therapeutic strategies for the combined treatment of diabetic periodontitis by regulating the autophagy pathway, and establish a theoretical foundation for the development of effective interventions.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7781-7794"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325980","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":"Role of Macrophage Polarization in Chronic Rhinosinusitis Based on the Yin-Yang Theory: A Review.","authors":"Fei Wang, Ye Xiong, Yaxian Zhu, Xiaoqian Yang, Kai Liu, Zhenhua Zhu","doi":"10.2147/JIR.S514060","DOIUrl":"10.2147/JIR.S514060","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis (CRS) is a prevalent otolaryngologic condition that markedly impacts patients' quality of life; however its pathogenesis is intricate and the clinical efficacy of known treatments remains limited.</p><p><strong>Methods: </strong>In recent years, there has been a growing focus on the role of immune function in the pathogenesis of CRS. Recent studies have revealed a correlation between macrophage polarization and CRS development. Macrophage polarization denotes distinct phenotypes of macrophages in diverse microenvironments, with the M1 and M2 phenotypes sharing similarities with the Yin-Yang concept of traditional Chinese medicine, encompassing mutual support and utilization, a balance between growth and elimination, and self-healing and equilibrium.</p><p><strong>Results: </strong>This study briefly reviews the latest research on traditional Chinese medicine compound prescriptions and the regulation of macrophage polarization by traditional Chinese medicine monomers, aligned with the main treatment principles of CRS, with the aim of offering novel directions and strategies for the clinical management of this condition.</p><p><strong>Conclusion: </strong>This study investigated the role of macrophage polarization in CRS from the perspective of the Yin-Yang Theory of traditional Chinese medicine.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7813-7825"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325979","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":"Research Progress on Th17/Treg Cell Imbalance in Epileptic Seizures.","authors":"Liu Mu, Yan Rong, Yang Jia Xin, Hong Zhang, Zucai Xu","doi":"10.2147/JIR.S524814","DOIUrl":"10.2147/JIR.S524814","url":null,"abstract":"<p><p>Epilepsy is associated with widespread neurological circumstances due to aberrant neuronal discharges in the brain, which have significant adverse effects on patient's quality of life and increase their risk of death. Immune imbalance, particularly disruption of the Th17/Treg cell balance, has gained increasing attention in the pathophysiology of epilepsy as our understanding of neuroimmune interactions improves. This paper examines the potential therapeutic effects and thoroughly discusses the processes by which the Th17/Treg cell imbalance contributes to the development of epilepsy. The primary emphasis is on the mechanism by which this imbalance impairs blood-brain barrier integrity, neuroinflammation, and other elements. On the therapeutic front, targeting the Th17/Treg axis for immune regulation-through approaches such as ketogenic diets, nanomaterials, and gene editing-shows promising prospects for restoring immune balance. By furthering our knowledge of the connection between Th17/Treg cell imbalance and epilepsy etiology, this work offers a crucial theoretical foundation for creating innovative immunotherapy approaches.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7769-7779"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325978","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":"Novel Proteomic Insights into Hip Fractures in the Elderly: Unraveling Immunologic Biomarkers, Temporal Expression Patterns, and Clinical Correlations.","authors":"Yining Lu, Jiaoran Liu, Wei Chen, Pan Hu, Yan Pei, Yiming Gao, Hairong Lu, Ling Wang, Yingze Zhang","doi":"10.2147/JIR.S513035","DOIUrl":"10.2147/JIR.S513035","url":null,"abstract":"<p><strong>Background: </strong>Hip fractures in the elderly triggers a severe inflammatory immune response.</p><p><strong>Methods: </strong>Peripheral blood samples from 16 elderly hip fracture patients and 16 healthy controls were analysed for 92 inflammatory biomarkers using proximity extension assay (PEA) at different stages after trauma.</p><p><strong>Results: </strong>Dynamic trends in inflammatory proteins after surgery were assessed. Correlation analyses showed significant associations between inflammation-related proteins and clinical parameters. A prognostic risk score model was developed: on day 1, CCL19, FGF-19 and MCP-2 were significant; on day 3, TGF-α, FGF-5, CCL19, IL-22RA1 and IL-12B were included; and on day 7, IL-2RB, CCL19 and 4E-BP1 were significant. High-risk patients had a significantly lower rate of recovery compared with low-risk patients.</p><p><strong>Conclusion: </strong>In this study, we have highlighted the complex inflammatory response during fracture healing and emphasised the importance of long-term monitoring of protein dynamics.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7703-7716"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317118","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":"Adipose-Derived Mesenchymal Stem Cells Accelerate Diabetic Foot Ulcer Healing by Promoting Macrophage M2 Polarization Through Downregulation of <i>EREG</i> and <i>CSTA</i>.","authors":"Jing Cao, Xin Zhang, Zhujun Li, Sen Zhang, Leiming Guo, Zichao Liu, Wenqiang An, Lijia Xu, Lijie Li, Xiao Long, Yuemei Yang","doi":"10.2147/JIR.S519713","DOIUrl":"10.2147/JIR.S519713","url":null,"abstract":"<p><strong>Purpose: </strong>Macrophage polarization plays a critical role in the chronic wound healing of diabetic foot ulcers (DFU). Recent studies have shown that adipose-derived mesenchymal stem cells (ADSCs) can reduce inflammation in DFU and promote wound healing. Despite advances in stem cell therapy, the molecular mechanisms by which ADSCs regulate macrophage polarization in DFU healing remain unclear, and robust prognostic models for DFU are lacking. This study aims to identify macrophage polarization-associated molecules in DFU and explore whether ADSCs promote DFU healing by regulating these molecules.</p><p><strong>Patients and methods: </strong>Macrophage polarization-associated differentially expressed genes (MA-DEGs) were screened from GSE134431 and GSE80178 datasets. Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Machine learning and Firth regression were employed to develop a prognostic model, which was evaluated using receiver operating characteristic (ROC) curves. The expression of predicted genes (<i>EREG</i> and <i>CSTA</i>) and the regulatory effects of ADSCs on these genes were validated in both DFU mouse model and THP-1 cells.</p><p><strong>Results: </strong>A total of 30 macrophage polarization-associated differentially expressed genes (MA-DEGs) were identified, including 18 hub genes. These MA-DEGs were primarily enriched in pathways related to leukocyte chemotaxis and interleukin-4 and 13. A two-gene prognostic model was constructed using machine learning and Firth regression, achieving an AUC greater than 0.944 in both the training and external validation datasets. In vivo and in vitro experiments demonstrated that ADSCs regulate <i>EREG</i> and <i>CSTA</i> expression to promote macrophage M2 polarization and facilitate DFU wound healing.</p><p><strong>Conclusion: </strong>This study elucidates the molecular mechanisms by which ADSCs facilitate DFU healing via macrophage M2 polarization. The identified two-gene MA-DEGs model not only serves as a potential prognostic biomarker but also provides promising targets for DFU therapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7749-7768"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317115","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":"<i>Arisaema cum</i> Bile Mitigate Febrile Seizure in Rats via Inhibition of Neuroinflammation, Regulation of FXR and GABA Signaling Pathway.","authors":"Xu Wu, Lian Zhong, Jing Wang, Qiao Zhang, Jing Sun, Changli Wang, Mengmeng Zhang, Chongbo Zhao","doi":"10.2147/JIR.S508690","DOIUrl":"10.2147/JIR.S508690","url":null,"abstract":"<p><strong>Background: </strong><i>Arisaema cum</i> bile (known as <i>DanNan Xing</i> in Chinese, DNX) is a traditional herbal medicine commonly used to treat febrile seizure (FS), but the underlying mechanism remains unclear.</p><p><strong>Objective: </strong>To evaluate the therapeutic effect of DNX on hot water bath-induced FS rat model and further explore the potential mechanism.</p><p><strong>Methods: </strong>The chemical constituents of DNX were determined via liquid chromatography-mass spectrometry (LC-MS). FS rat model was established using a hot water bath (45 ± 2 °C), and DNX (2.8 and 0.7 g/kg, i.g) were administered for two weeks. Based on behavior test (duration and latency), pathological changes in the hippocampal tissue, and the levels of inflammatory cytokines the therapeutic effect of DNX for FS was evaluated. Subsequently, the network pharmacology, 16S rRNA and non-targeted metabolomics analysis were combined analysis to explore the potential signaling pathway. Furthermore, the signaling pathway was verified using the RT-qPCR and immunohistochemistry assay.</p><p><strong>Results: </strong>The DNX treatment showed effective therapy on hot water bath induced FS, as indicated by a shortened seizure duration time, prolonged seizure latency, reduced hippocampal neuron damage and neuroinflammatory factor levels (TNF-α, IL-1β, IL-6, and HMGB1). Neurotransmitters (GABA, Glu) are also significantly regulated. Moreover, the relative abundance of <i>Lactobacillus</i> and <i>Lachnospiraceae</i> was notably increased (<i>p</i> < 0.01), while that of <i>Tenericutes</i> decreased, compared to gut microbiota of FS rat. A total of 20 fecal differential metabolites were regarded as the potential biomarkers including GABA, CDCA, and UDCA for anti-FS of DNX, and combined network pharmacy the metabolic pathways of primary bile acids (BAs) biosynthesis and alanine, aspartate and glutamate metabolism were involved.</p><p><strong>Conclusion: </strong>DNX possesses a therapeutic effect on FS through inhibiting neuroinflammation and regulation of FXR and GABA signaling pathway.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"7683-7701"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317114","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}