{"title":"Integrative Bulk and Single-Cell Transcriptomic Profiling Reveals Oxidative Stress-Related Genes and Potential Therapeutic Targets in Osteoarthritis.","authors":"Jinhui Peng, Jinzhong Chen, Duan Gao, Bowei Liang, Zongquan Huang, Bo Xiong, Shuheng Zhou, Guanghai Tan, Zhihui Zhong, Xianghong Zeng","doi":"10.1155/mi/1240226","DOIUrl":"https://doi.org/10.1155/mi/1240226","url":null,"abstract":"<p><p>Osteoarthritis (OA) is increasingly recognized as a degenerative joint disease that leads to a serious problem of public health, yet the underlying molecular mechanisms remain incompletely understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets from the Gene Expression Omnibus (GEO) to systematically investigate oxidative stress-related genes and pathways in OA. Gene set enrichment analysis (GSEA) revealed significant activation of oxidative stress signaling in OA cartilage tissues, with 58 differentially expressed oxidative stress-related genes identified. Subsequent LASSO regression analysis highlighted seven diagnostic genes (STC2, LSP1, COL6A1, FOS, SELENON, TP53, and HSPA8), which demonstrated robust diagnostic performance in both training and validation cohorts. Single-cell analysis further revealed cell-type-specific differences in oxidative stress activity, with homeostatic chondrocytes (HomCs) exhibiting the highest pathway scores. Among the identified genes, FOS emerged as a hub regulator, showing elevated expression in HomCs from OA samples and strong associations with immune infiltration and proinflammatory pathways. Functional assays demonstrated that FOS knockdown significantly attenuated IL-1β-induced oxidative stress, apoptosis, and inflammatory cytokine (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) release in chondrocytes. Furthermore, molecular docking and dynamics simulations identified ursolic acid (UA) as a stable small-molecule FOS binder, and in vitro experiments confirmed its inhibitory effects on oxidative stress and inflammation, comparable to FOS silencing or pharmacological inhibition. Collectively, our findings suggest that oxidative stress-related genes, particularly FOS, play a central role in OA pathogenesis by linking redox imbalance to immune dysregulation and chondrocyte injury, and highlight UA as a potential therapeutic candidate for OA management.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1240226"},"PeriodicalIF":4.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhifen Han, Yi Yuan, Min Hu, Jinxiang Wang, Bing Gao, Xiaoxi Sha
{"title":"Identification and Characterization of Cytokine Genes in Breast Cancer for Predicting Clinical Outcomes.","authors":"Zhifen Han, Yi Yuan, Min Hu, Jinxiang Wang, Bing Gao, Xiaoxi Sha","doi":"10.1155/mi/8441796","DOIUrl":"https://doi.org/10.1155/mi/8441796","url":null,"abstract":"<p><p>Breast cancer is a highly heterogeneous disease with diverse clinical outcomes and treatment responses. While traditional molecular subtypes have improved patient stratification, they fail to fully capture the immune heterogeneity that influences tumor progression and therapy efficacy. Cytokines play a central role in regulating immune responses within the tumor microenvironment, yet their systematic profiling in breast cancer remains unexplored. Here we conducted a comprehensive analysis of cytokine expression across breast cancer patients using transcriptomic and clinical data. Prognostic cytokines were identified via survival analysis, and a cytokine-based molecular classification was established through consensus clustering. We identified three cytokine-driven breast cancer subtypes with distinct transcriptional profiles, immune infiltration patterns, and clinical outcomes. A cytokine-derived risk score was then developed using lasso regression and validated in external datasets to assess its predictive power for patient survival and treatment response. We then characterized the immune microenvironment of patients with different risk scores using immune infiltration analysis and single-cell RNA sequencing (RNA-seq) data. The risk score effectively stratified patients into high- and low-risk groups, with significant differences in survival outcomes. The low-risk subtype exhibited enhanced immune cell infiltration and stronger immune cell interactions, while the high-risk subtype was associated with an immunosuppressive microenvironment and a worse prognosis. Notably, patients with low-risk scores demonstrated superior responses to both immunotherapy and chemotherapy, highlighting the clinical relevance of cytokine-based classification. Our study provides the first comprehensive cytokine-based molecular subtyping of breast cancer, revealing distinct immune landscapes and prognostic implications. The cytokine-derived risk score offers a powerful tool for predicting patient survival and treatment response, with potential applications in personalized medicine and immunotherapy strategies. These findings underscore the critical role of cytokines in shaping breast cancer heterogeneity and highlight their value as biomarkers for therapeutic decision-making.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8441796"},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12530932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Calcitriol Administration Attenuates Acute Lung Injury by Improving Angiopoietin/Tie2 Dysregulation and Alveolar-Capillary Barrier Integrity in a Mouse Model of Ovariectomy Complicated With Sepsis.","authors":"Chiu-Li Yeh, Shang-Ming Tseng, Mei-Pei Huang, Wei-Hsin Lin, Ting-Chun Kuo, Jin-Ming Wu, Kuen-Yuan Chen, Ming-Hsun Wu, Po-Jen Yang, Po-Chu Lee, Chien-Chia Chen, Chih-Yuan Lee, Sung-Ling Yeh, Ming-Tsan Lin","doi":"10.1155/mi/4374164","DOIUrl":"10.1155/mi/4374164","url":null,"abstract":"<p><p>Menopause is associated with excessive weight, increased systemic inflammation, and oxidative stress. Menopause with obesity may aggravate the severity of organ damage when complicated with sepsis. This study investigated the impacts of calcitriol on acute lung injury (ALI)-associated angiopoietin (Ang)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domain 2 (Tie2) dysregulation, impairment of the barrier integrity, and ion disturbance in ovariectomized mice with sepsis. 6-month-old female C57BL/6 mice were divided into three groups: the OB group, which contained mice with a sham ovariectomy and high-fat diet (HFD); the OVSS group, which contained mice with an ovariectomy, an HFD, cecal ligation and puncture (CLP), and an intravenous saline injection after CLP; and the OVSD group, which contained mice with an ovariectomy, an HFD, CLP, and a calcitriol injection. The HFD was fed for 12 weeks. Mice in the respective groups were sacrificed on 24 or 72 h after CLP. Results showed that compared to the OB group, the OVSS group had higher oxidative stress, iron and copper overload, whereas the Ang1/Ang2 ratio and tight junction (TJ) protein levels were lower in the lungs. Calcitriol treatment in mice with ovariectomy and CLP enhanced Tie2 levels and the Ang1/Ang2 ratio, increased zona occludens (ZOs)-1, occludin, and claudin-5 levels. Elevated reduced glutathione (GSH) levels and glutathione peroxidase 4 (GPX4) activities, reduced iron and copper contents, and suppressed ferroptosis- and cuproptosis-associated components were found in the lungs. Also, higher survival rates and lower lung injury scores were noted in the OVSD groups. These findings suggest that calcitriol treatment mitigated the dysregulated Ang/Tie2 pathway, improved the integrity of the alveolar-capillary barrier, elicited a more balanced redox status, alleviated ferroptosis and cuproptosis in the lungs in an ovariectomy model complicated with sepsis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4374164"},"PeriodicalIF":4.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12520812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhilin Miao, Yamki Leung, Yuqing Fu, Li Luo, Quan Liu, Jianbo Liao, Jiatang Xu, Qingyang Song, Suiqing Huang, Zhongkai Wu
{"title":"The Dual Role of Macrophages in MIRI and MI by Immunity and Inflammation: Damage, Repair, Crosstalk, and Therapy.","authors":"Zhilin Miao, Yamki Leung, Yuqing Fu, Li Luo, Quan Liu, Jianbo Liao, Jiatang Xu, Qingyang Song, Suiqing Huang, Zhongkai Wu","doi":"10.1155/mi/9912957","DOIUrl":"10.1155/mi/9912957","url":null,"abstract":"<p><p>The global prevalence of coronary artery disease (CAD) continues to escalate globally. A substantial proportion of CAD patients develop myocardial ischemic injury or myocardial infarction (MI), while reperfusion therapy paradoxically induces myocardial ischemia/reperfusion injury (MIRI). Tissue-resident and recruited macrophages critically orchestrate cardiac inflammation resolution and repair-remodeling processes. Pathogenically, MIRI features early explosive inflammation with secondary reperfusion injury, whereas MI progresses from acute inflammation to reparative fibrosis. We highlight two pivotal macrophage subsets-C─C chemokine receptor type 2 (CCR2)<sup>high</sup> macrophages dominating early MI phases and triggering receptor expressed on myeloid cells 2 (TREM2)<sup>high</sup> macrophages prevailing in late stages-exploring their distinct roles in both MI and MIRI. This includes examining macrophage crosstalk with neutrophils and other immune-inflammatory cells. Finally, we discuss macrophage-targeted therapies encompassing anti-inflammatory modulation, exosome-mediated delivery, and stem cell interventions to mitigate cardiac injury progression.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9912957"},"PeriodicalIF":4.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification and Validation of Pyroptosis-Associated Gene Signature in Primary Sjögren's Syndrome.","authors":"Yijun Dai, Hanzhi Chen, Meng Zhou, Chenmin Wu, Fei Gao, Yingzheng Wang, Qing Yan, Zuoan Li","doi":"10.1155/mi/1538054","DOIUrl":"10.1155/mi/1538054","url":null,"abstract":"<p><strong>Background: </strong>Pyroptosis, a form of programmed cell death, has been implicated in autoimmune diseases (ADs) pathogenesis. However, its role in primary Sjögren's syndrome (pSS) remains unclear. This study aims to identify pyroptosis-related gene (PRG) signatures in pSS.</p><p><strong>Methods: </strong>Three datasets were obtained from the Gene Expression Omnibus (GEO) database to analyze the gene expression profiles in pSS. Differentially expressed genes (DEGs) were intersected with PRGs to identify pyroptosis-related DEGs (PRDEGs). Functional enrichment was assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Key genes were identified using the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) analyses. A diagnostic model was constructed using logistic regression. mRNA-microRNA (miRNA) and mRNA-transcription factor (TF) interaction networks were constructed. Immune cell infiltration (ICI) was analyzed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORTs) and single-sample gene set enrichment analysis (ssGSEA). Experimental validation was performed in nonobese diabetic (NOD)/ShiLtj mice using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunofluorescence and was further validated using immunofluorescence in pSS patient samples.</p><p><strong>Results: </strong>A total of 489 DEGs were identified, of which 22 were pyroptosis-related. GO/KEGG analysis revealed enrichment in immune response regulation, pyroptosis, and the positive regulation of receptor signaling pathways. LASSO and SVM analyses identified eight key genes (<i>CRTAC1</i>, platelet-endothelial cell adhesion molecule-1 [<i>PECAM1</i>], <i>IRF2</i>, <i>GZMA</i>, <i>IFI16</i>, absent in melanoma 2 [<i>AIM2</i>], <i>TNF</i>, and macrophage-expressed gene 1 [<i>MPEG1</i>]), which were incorporated into a diagnostic model that demonstrated strong discriminatory performance in both combined and validation datasets. Experimental validation confirmed significant increased expressions of <i>PECAM1</i>, <i>IFI16</i>, <i>AIM2</i>, and <i>MPEG1</i> in the salivary glands from both NOD mice and pSS patients.</p><p><strong>Conclusions: </strong>PECAM1, IFI16, AIM2, and MPEG1 were identified as PRG signatures and potential biomarkers in pSS, providing novel insights into pSS pathogenesis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1538054"},"PeriodicalIF":4.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association Between the CALLY Index and Kidney Stones: Insights From NHANES 2007-2010.","authors":"Liangliang Dai, Chenjie Qiu","doi":"10.1155/mi/9920716","DOIUrl":"10.1155/mi/9920716","url":null,"abstract":"<p><strong>Background: </strong>Kidney stones are a prevalent health concern with rising incidence, influenced by factors such as inflammation, nutrition, and immune function. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index-a composite measure of CRP, albumin, and lymphocyte count-has demonstrated prognostic value in several cancers. However, its relevance to kidney stone formation remains largely unexplored. This study aimed to examine the association between the CALLY index and kidney stone risk using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010.</p><p><strong>Methods: </strong>A total of 10,562 participants were included after applying exclusion criteria. Kidney stone status was determined through self-reported questionnaires, and the CALLY index was calculated accordingly. Associations between the CALLY index and kidney stones were assessed using multivariable logistic regression, restricted cubic spline (RCS) models, and subgroup analyses.</p><p><strong>Results: </strong>Participants with kidney stones exhibited a lower mean CALLY index. Multivariable analyses revealed a significant inverse association between the CALLY index and kidney stone risk, particularly when the index was modeled categorically. Individuals in the highest quartile of the CALLY index had a 27.3% lower risk of kidney stones compared with those in the lowest quartile. RCS analysis further confirmed a nonlinear relationship.</p><p><strong>Conclusion: </strong>The findings suggest that the CALLY index is negatively associated with kidney stone risk.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9920716"},"PeriodicalIF":4.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacological and Pharmacokinetic Insights Into Columbianadin: A Promising Natural Anti-Inflammatory Compound.","authors":"Yusong Wang, Le Tang, Jia Miao, Shouxiang Cheng, Yanqing Xu, Wen Xie","doi":"10.1155/mi/6284834","DOIUrl":"10.1155/mi/6284834","url":null,"abstract":"<p><p>Columbianadin (CBN), a dihydroangelic acid ester and a naturally occurring coumarin compound, is primarily derived from plants in the <i>Apiaceae</i> family, notably the traditional Chinese medicinal herb <i>Angelica pubescens</i>. Modern pharmacological research has revealed that CBN exhibits a broad spectrum of bioactivities, including neuroprotective, antitumor, anti-inflammatory, antiarthritic, and analgesic effects. As a key bioactive constituent of <i>Angelica pubescens</i>, CBN demonstrates superior therapeutic potential compared to its source plant, attributed to its distinctive chemical structure and multitarget regulatory mechanisms. This review systematically summarizes the pharmacological properties and underlying molecular mechanisms of CBN, with a special emphasis on its emerging role in modulating inflammation and treating rheumatoid arthritis (RA) and related disorders. Additionally, the pharmacokinetic (PK) characteristics of CBN are discussed to support its potential development as a novel drug candidate. This work aims to provide a theoretical foundation for the rational design of natural product-based therapeutics and to promote the translational research and clinical application of CBN.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6284834"},"PeriodicalIF":4.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptomic and Polysomnographic Insights Into Core Signaling Pathways in Obstructive Sleep Apnea.","authors":"Peijun Liu, Xiaolan Yang, Guang Cai Li","doi":"10.1155/mi/4579543","DOIUrl":"10.1155/mi/4579543","url":null,"abstract":"<p><p><b>Background:</b> This study integrates transcriptomics and polysomnography (PSG) to investigate the core signaling pathways underlying obstructive sleep apnea (OSA), aiming to elucidate its complex pathophysiological mechanisms. These findings may provide new perspectives on the prevention, diagnosis, and treatment of OSA. <b>Methods:</b> Participants underwent PSG to monitor indicators, such as total sleep time, apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and lowest oxygen saturation (LSO<sub>2</sub>). Individuals with AHI > 5 were categorised into the OSA group, while others were classified as the regular snoring group. Total RNA from white blood cells was extracted using the TRIzol method, and transcriptomic data were obtained via high-throughput sequencing. Weighted Gene Coexpression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) network analysis were used to identify OSA-related core genes. Differential gene expression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore key signaling pathways. Single-cell sequencing validated the findings, and Mendelian randomization (MR) analysis confirmed causal links between genes and pathways. <b>Results:</b> While no significant differences were observed between the OSA and regular snoring groups in gender, age, or body mass index (BMI), significant disparities were noted in sleep parameters such as AHI, ODI, and LSO<sub>2</sub>. Principal component analysis (PCA) revealed transcriptomic differences between the groups. WGCNA identified 302 differentially expressed genes (DEGs), with the Palevioletred module significantly correlating with PSG parameters. GO and KEGG analyses implicated core genes in regulating inflammation, viral defence, cell growth, and apoptosis, highlighting the NF-κB signaling pathway as central to OSA pathogenesis. PPI analysis identified key genes, including CEBPB and SPI1, while single-cell sequencing suggested NF-κB pathway activation affecting T cell subgroup distribution. MR confirmed causal relationships between core genes and the NF-κB pathway. <b>Conclusion:</b> This study identified significant differences in sleep parameters between OSA and regular snoring groups and revealed core genes enriched in the NF-κB signaling pathway. These findings suggest that targeting the NF-κB pathway may offer therapeutic benefits for OSA.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4579543"},"PeriodicalIF":4.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating the Association Between Neutrophil Gelatinase-Associated Lipocalin Levels and Periodontal Health Status in Patients With Chronic Kidney Disease.","authors":"Ahmed Mutar, Maha Sh Mahmood","doi":"10.1155/mi/4114758","DOIUrl":"10.1155/mi/4114758","url":null,"abstract":"<p><p><b>Background:</b> Chronic kidney disease (CKD) is one of the significant public health problems that is characterized by structural and functional changes due to various causes. Periodontal disease has risen as a nontraditional risk factor for CKD since it is considered a source of inflammatory products in systemic disease. <b>Objective:</b> The objective of the study was to investigate the association between serum and salivary levels of neutrophil gelatinase-associated lipocalin (NGAL) and the periodontal health status of patients with CKD. <b>Methodology:</b> A cross-sectional study was carried out to achieve the goal. It involved 150 adult patients with CKD, with and without hemodialysis (HD). Assessment of the periodontal health status was done through the measurement of periodontal parameters. Moreover, samples of saliva and serum were collected from each patient and examined for NGAL levels using an enzyme-linked immunosorbent test. <b>Results:</b> The study findings illustrated a significant elevation in the mean concentration of NGAL in saliva in comparison to serum in both groups (saliva 540.554 ± 100.595 ng/mL, 458.134 ± 99.450 ng/mL) versus serum (274.138 ± 70.18 ng/mL, 351.66 ± 99.451 ng/mL) (<i>p</i> < 0.001). As well as significant elevation of the biomarker was also pronounced in the saliva of the CKD group not on HD in comparison with the HD group (540.554 ± 100.595 ng/mL) versus (458.134 ± 99.450 ng/mL), respectively, <i>p</i>-value < 0.001. Regarding periodontal health status, findings showed that from the total sample of patients comprising 150 patients, the majority of them had periodontitis (42%) in the non-HD group and (38.6%) in the HD group (total 80.6%) while the prevalence of gingivitis was (8%) in non-HD group and (11.3%) in HD group (total 19.3%). In addition, results revealed a significant association of serum and salivary levels of NGAL with patients who have CKD on HD. On the other hand, the association with periodontal parameters was only clarified with the salivary level of NGAL. <b>Conclusion:</b> Elevated NGAL levels in saliva were significantly associated with CKD patients on HD as well as with clinical periodontal parameters.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4114758"},"PeriodicalIF":4.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}