Mediators of Inflammation最新文献

{"title":"Development of a Starvation Response-Based Model and Its Application in Prognostic Assessment of Liver Hepatocellular Carcinoma.","authors":"Xinjun Hu, Yafeng Liu, Shujun Zhang, Kaijie Liu, Xinyu Gu","doi":"10.1155/mi/8828435","DOIUrl":"10.1155/mi/8828435","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (LIHC) is a highly prevalent and poorly prognostic malignancy worldwide, and nutrient deprivation in the tumor microenvironment activates the starvation response in tumor cells. Starvation response-related genes (SRRGs) play critical roles in maintaining energy metabolism and promoting tumor development, but their value in prognostic prediction of LIHC has not been clarified. <b>Methods:</b> We based on public databases to obtain transcriptome and single-cell RNA sequencing (scRNA-seq) data for LIHC and SRRG from previous studies. Key modules relevant to SRRGs were identified by weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis was conducted using clusterProfiler R package. Independent prognostic genes were screened to build a RiskScore model and its performance was further verified. The immune microenvironmental profile of patients in different risk groups was assessed using the single-sample gene set enrichment analysis (ssGSEA), MCP-Counter, ESTIMATE, and TIMER algorithms. Seurat package for single-cell profiling and validation of key gene expression based on Huh7 and transformed human liver epithelial-2 (THLE-2) cell lines. The LIHC cell migration and invasion were measured by conducting wound healing and transwell assays. <b>Results:</b> The key module identified by WGCNA showed the strongest correlation with SRRGs and the glycolysis-related SRRGs were mainly enriched in metabolism-correlated pathways. Two protective genes (FBXL5 and PON1) and three risk genes (TFF2, TBC1D30, and SLC2A1) were discovered as the independent prognostic genes for LIHC. Activation of cytokine-cytokine receptor interaction and IL-17 signaling pathway and higher infiltration of immune cells in high-risk group was observed. The five independent prognostic genes were mainly expressed in cancer stem cells and epithelial cells, in particular, <i>SLC2A1</i> and <i>TFF2</i> were significantly high-expressed in epithelial cells in the tumor group than in nontumor group. <i>FBXL5</i> and <i>PON1</i> were downregulated, while <i>TFF2</i>, <i>TBC1D30</i>, and <i>SLC2A1</i> were upregulated in LIHC cells. Silencing SLC2A1 significantly inhibited LIHC cell migration and invasion. <b>Conclusion:</b> In this study, we constructed the first risk model based on SRRGs to accurately predict the prognosis of LIHC, which provides a new idea for individualized treatment and targeted intervention.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8828435"},"PeriodicalIF":4.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637425","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":"Evaluation of Gene Expression and the Regulatory Role of microRNAs Related to the Mitogen-Activated Protein Kinase Signaling Pathway in Human Retinal Pigment Epithelial Cells Treated With Lipopolysaccharide A and Tacrolimus.","authors":"Aleksandra Kiełbasińska, Katarzyna Krysik, Dominika Janiszewska-Bil, Martyna Machaj, Zuzanna Lelek, Mariola Szulik, Patrycja Mickiewicz, Anita Lyssek-Boroń, Beniamin Oskar Grabarek","doi":"10.1155/mi/8586711","DOIUrl":"10.1155/mi/8586711","url":null,"abstract":"<p><p><b>Background:</b> The retinal pigment epithelium (RPE) is central to retinal health and immune regulation. In diseases, such as proliferative vitreoretinopathy (PVR), dysregulated RPE function, driven by aberrant signaling pathways like mitogen-activated protein kinase (MAPK), contributes to fibrotic membrane formation and retinal detachment. Tacrolimus, an immunosuppressive agent, has shown potential to modulate signaling beyond immune cells, but its effect on MAPK signaling in RPE cells remains unclear. This study aimed to investigate the impact of tacrolimus on MAPK pathway gene expression and microRNA (miRNA)-mediated regulation in human RPE (H-RPE) cells under inflammatory conditions induced by lipopolysaccharide (LPS). <b>Methods:</b> H-RPE cells were treated with LPS and tacrolimus, and cell viability was evaluated by 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Transcriptomic profiling of 300 MAPK-related genes and corresponding miRNAs was performed using Affymetrix microarrays. Key targets were validated via quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Gene interaction networks were analyzed with STRING. <b>Results:</b> LPS significantly suppressed MAPK pathway gene and protein expression, including transforming growth factor beta 1 (TGF-β-1), mitogen-activated protein kinase kinase 7 (MAP2K7), mitogen-activated protein kinase 3 (MAPK3), and dual specificity phosphatase 4 (DUSP4). Tacrolimus reversed these effects in a time-dependent manner, restoring expression levels and modulating regulatory miRNAs (e.g., miR-3196, miR-27a/b-3p, miR-190a-3p, miR-149-3p). STRING analysis revealed a highly connected protein network, with MAPK3, MAPK8, and TRAF6 acting as central nodes. <b>Conclusion:</b> Tacrolimus modulates MAPK signaling in H-RPE cells by reversing LPS-induced suppression and regulating specific miRNAs. These findings suggest a potential therapeutic role for tacrolimus in mitigating inflammatory and fibrotic responses associated with PVR.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8586711"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591603","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 Dietary Inflammatory Index and NAFLD: A Cross-Sectional Study of the National Health and Nutrition Examination Survey.","authors":"Yuan He, Yuhang Yang, Pengfei Cheng, Wei Zhang, Jinghan Jia, Dawei Ye, Jinxi Wang","doi":"10.1155/mi/4954551","DOIUrl":"10.1155/mi/4954551","url":null,"abstract":"<p><p><b>Background and Aim:</b> The aim of this study was to determine if there is an association between the dietary inflammatory index (DII) and nonalcoholic fatty liver disease (NAFLD). <b>Methods:</b> Study data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Multiple logistic regression models were used to assess the association between DII and NAFLD. A restricted cubic spline (RCS) was used to investigate the non-linear association between DII and NAFLD. A total of 8708 people were included, with no age limit. <b>Results:</b> In fully adjusted multiple regression models, DII < 0 was associated with fewer incident NAFLD events compared with DII ≥ 0. In the RCS model, there was a positive nonlinear relationship between DII and NAFLD. In addition, the main positive association between DII and NAFLD was found in participants aged ≥60 years and who were white females. <b>Conclusions:</b> A proinflammatory diet is associated with the development of NAFLD, and we recommend improving diet to reduce the risk of developing liver disease, especially NAFLD.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4954551"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591602","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 Domain-Specific Physical Activity and Novel Inflammatory Biomarkers Among US Adults: Insights From NHANES 2007-2018.","authors":"Xin-Ying Liu, Kai Yao","doi":"10.1155/mi/1989715","DOIUrl":"10.1155/mi/1989715","url":null,"abstract":"<p><p><b>Objectives:</b> The novel inflammatory biomarkers, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and neutrophil-to-lymphocyte ratio (NLR), can contribute to predicting the future risk of various diseases. However, the impact of different physical activity (PA) domains on systemic inflammation remains unclear. The study aims to investigate the relationship between domain-specific moderate-to-vigorous-intensity PA (MVPA) and these inflammatory biomarkers among US adults. <b>Methods:</b> Participants from the US National Health and Nutrition Examination Survey (NHANES) (2007-2018) were included in this study. The Global Physical Activity Questionnaire was used to assess self-reported MVPA. MVPA was categorized into three domains, including occupation-related MVPA (O-MVPA), transportation-related MVPA (T-MVPA), and leisure-time-related MVPA (LT-MVPA). SII, SIRI, and NLR were derived from the complete blood count results obtained at the NHANES Mobile Examination Centers (MEC). Weighted multivariable linear regression and propensity score matching (PSM) were used to examine the relationship between domain-specific MVPA and inflammatory biomarkers. Additionally, stratified and mediation analyses were performed to assess potential effect modifications and mediators in this association. <b>Results:</b> The study included a total of 29,072 participants. Following PSM, weighted multivariable linear regression indicated a negative association between LT-MVPA meeting PA guidelines ( ≥ 150 min/week) and circulating inflammatory biomarkers (<i>β</i> = -36, 95% confidence interval [CI]: -47 to -25, <i>p</i>  < 0.001 for SII; <i>β</i> = -0.09, 95% CI: -0.13 to -0.05, <i>p</i>  < 0.001 for SIRI; <i>β</i> = -0.08, 95% CI: -0.11 to -0.05, <i>p</i>  < 0.001 for NLR, respectively), adjusting for all potential covariates in model 2. Participants engaging in sufficient T-MVPA (≥ 150 min/week) also exhibited lower SII and SIRI levels (<i>β</i> = -17, 95% CI: -32 to -2.4, <i>p</i>=0.023; <i>β</i> = -0.07, 95% CI: -0.11 to -0.03, <i>p</i>=0.002). Conversely, O-MVPA showed no significant correlation with any inflammatory biomarkers (all <i>p</i>  > 0.05). No significant effect modification was observed in the association between LT-MVPA or T-MVPA and inflammatory biomarkers (SII, SIRI, and NLR). Mediation analysis showed that body mass index (BMI) mediated the relationships between these inflammatory biomarkers and both LT-MVPA and T-MVPA. <b>Conclusions:</b> The impact of different PA domains on systemic inflammation varies significantly. Given the well-established link between chronic inflammation and diseases such as cardiovascular disease (CVD), diabetes, and metabolic disorders, specific recommendations for PA categories should be provided, particularly targeting individuals with high systemic inflammatory responses.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1989715"},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540807","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":"Prognostic Significance of the Serum Creatinine Level During the Shock Stage in Severe Burn Patients: A 10-Year Retrospective Study.","authors":"Wei Zhu, Xiaorong Xie, Ziqin Shu, Li Li, Gaozhong Hu, Huapei Song","doi":"10.1155/mi/8876691","DOIUrl":"10.1155/mi/8876691","url":null,"abstract":"<p><p><b>Objective:</b> To evaluate the significance of serum creatinine (Scr) level during the shock stage as a prognostic indicator for 90-day mortality in severe burn patients. <b>Methods:</b> This retrospective cohort study included 224 severe burn patients with a burn ≥50% total body surface area (TBSA) admitted to the First Affiliated Hospital of Army Medical University from January 1, 2014, to December 31, 2023. Patient demography, the burn severity, infection markers, protein levels, renal function indicators, and prognostic indicators, including the hospital 90-day mortality rate, were collected. The comparisons of these indicators between the survival and death groups were performed by means of the independent-samples Mann-Whitney <i>U</i> test and chi-square test. Then the significantly different indicators between the two groups were subjected to univariate and multivariate logistic regression analyses. The independent risk factors affecting the prognosis of severe burn patients during the shock stage were screened, and a nomogram for the prediction of the survival rate of severe burn patients was constructed using the indicators in the shock stage. A receiver operating characteristic (ROC) curve was drawn to obtain the corresponding cut-off value. Differences between the two groups of patients separated according to the cut-off value were analyzed. The difference between the survival rate of both groups of patients during hospitalization was analyzed using the Kaplan-Meier(K-M) curve. <b>Results:</b> The survival rate was 183/224 with total length of stay (LOS) in hospital of 66 days (27-113). The differences in TBSA, burn index (BI), infection indicators (leukocytes, C-reactive protein [CRP], and procalcitonin [PCT]), and renal function indicators (Scr, blood urea nitrogen [BUN], and cystatin C [CysC]) between the survival group and the death group were significant (<i>p</i>  < 0.05). Logistic regression analysis revealed that the Scr level during the shock stage was an independent risk factor for the prognosis of the risk of death in severe burn patients with a cut-off value of 100 μmol/L. Compared with the low-Scr group (Scr < 100 μmol/L), the high-Scr group (Scr ≥ 100 μmol/L) had a larger TBSA and higher BI. The Scr level was positively correlated with the increase in the TBSA and BI. The development of persistent organ dysfunction (POD) and mortality in the high-Scr group was significantly greater than those in the low-Scr group. <b>Conclusion:</b> The Scr level during the shock stage is an independent risk factor for hospital death, which is important for the prognosis of the 90-days' mortality of severe burn patients, in combination with patient age, TBSA, and BI.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8876691"},"PeriodicalIF":4.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528656","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":"Analysis of the Correlation Between MDS Inflammatory Indicators and Clinical Characteristics: A Comprehensive Analysis.","authors":"ZhongLi Hu, Lijia Pei, ZhongTing Hu, YanLi Yang, YuXian Wang, Mengqing Hua, Ping Zhao","doi":"10.1155/mi/8812329","DOIUrl":"10.1155/mi/8812329","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to investigate the correlations among the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) at the initial diagnosis of myelodysplastic syndrome (MDS) and the clinical characteristics of patients. It explores the correlation between MDS and inflammatory markers, providing a basis for early assessment of treatment efficacy, diagnosis, and guiding personalized treatment. <b>Methods:</b> Analyzing the bone marrow smears and flow cytometry immunophenotyping of 70 MDS patients. Conducting a comparative analysis of the multi-parameter linear correlation between the clinical characteristics of MDS patients and inflammatory markers, comparing the differences in inflammatory markers between MDS patients and the control group. Additionally, investigating the differential correlation analysis between different primitive cell ratios, different MDS types, different immunophenotypic characteristics, different morphological features, and inflammatory markers. <b>Results:</b> Comparative analysis between MDS and the control group revealed that NLR and PLR have good diagnostic specificity (area under the curve [AUC] = 0.9169, 0.8312). When comparing the clinical characteristics of MDS patients, MLR showed a strong correlation with the total white blood cell count at the initial diagnosis (<i>r</i> = 0.661, <i>p</i> = 0.0004), while NLR demonstrated a correlation with lactate dehydrogenase (LDH; <i>r</i> = 0.313, <i>p</i> = 0.037). In different WHO-classified MDS groups, there are significant differences in the comparison of three groups of inflammatory markers between the groups. The MDS group with specific immunophenotypic characteristics displayed significant differences in PLR compared to the group without specific immunophenotypic characteristics. Additionally, CD34 proportion exhibited a negative correlation with NLR index (<i>r</i> = -0.296, <i>p</i> = 0.0129). And patients with low PLR index have a higher survival time than those with high PLR index (<i>p</i> = 0.007). <b>Conclusion:</b> Inflammatory markers are correlated with the clinical characteristics of MDS, providing not only auxiliary evidence for the clinical diagnosis of MDS but also showing differences in inflammatory markers based on different tumor burdens in MDS. This serves as a reference for the treatment strategy of inhibiting the progression of MDS to acute leukemia by reversing the inflammatory trend.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8812329"},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506404","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":"Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches.","authors":"Hiral Aghara, Manali Patel, Prashsti Chadha, Kirti Parwani, Ruchi Chaturvedi, Palash Mandal","doi":"10.1155/mi/6733477","DOIUrl":"10.1155/mi/6733477","url":null,"abstract":"<p><p>The gut-liver-brain axis (GLB axis) plays a crucial role in maintaining metabolic, immune, and neurological homeostasis. The gut microbiota influences systemic health through its metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) derivatives, which regulate immune function, lipid metabolism, and neurotransmitter balance. Dysbiosis is an imbalance in gut microbiota that has been implicated in metabolic dysfuntion associated fatty liver disease (MAFLD), alcohol-associated liver disease (AALD), and neuroinflammatory conditions such as schizophrenia. Increased gut permeability allows microbial byproducts like lipopolysaccharides (LPSs) to enter the liver and brain, activating inflammatory pathways that contribute to disease progression. Moreover, hepatic dysfunction can lead to neuroinflammation and cognitive impairments. Understanding the interplay between microbial metabolites and host physiology provides insight into novel therapeutic interventions. Strategies such as probiotics, prebiotics, synbiotics, fecal microbiota transfer (FMT), and postbiotics offer potential treatments to restore gut eubiosis and mitigate disease severity. This review highlights the mechanistic role of the GLB axis in health and disease, emphasizing microbiome-targeted therapies as a promising avenue for managing metabolic and neuropsychiatric disorders. <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04823676, NCT02496390, NCT06024681, NCT02721264.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6733477"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497471","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":"WTAP Accelerates Exhaustion of CD8⁺ T Cells and Progression of Hepatocellular Carcinoma by Promoting m6A Modification and Translation of PD1 mRNA.","authors":"Rong Li, Shunle Li, Hua Li, Bingli Liu, Zimu Wang, Huanqin Lei, Yuting Li, Lijuan Jia, Junhui Li, Hongwei Lu, Meng Xu","doi":"10.1155/mi/6217272","DOIUrl":"10.1155/mi/6217272","url":null,"abstract":"<p><p>The N6-methyladenosine (m6A) methylase WTAP has been identified as a proto-oncogene in multiple cancers, including hepatocellular carcinoma (HCC). Interestingly, although WTAP expression does not differ between normal liver and HCC tissues or across different stages of HCC, patients with higher WTAP expression exhibit significantly shorter median survival times (MSTs). Here, we found that WTAP was upregulated in tumor-infiltrating CD8⁺ T cells, which were more enriched in HCC patients compared to the controls. HCC patients also displayed higher PD1 levels and a greater proportion of exhausted CD8⁺ T cells (TCF⁺ PD1⁺). Moreover, WTAP promoted PD1 expression and suppressed the proliferation and immune activity of CD8⁺ T cells. In the co-culture system, WTAP-overexpressing CD8⁺ T cells enhanced the malignancy of HCC cells. Notably, WTAP silencing further augmented the boosting effect of PD1 silencing on CD8⁺ T cell immune activity and strengthened its inhibitory effect on HCC cell growth. As an m6A \"writer\", WTAP increased the m6A level of PD1 mRNA, thereby promoting YTHDF1-mediated translation of PD1. Finally, in the HuNSG xenograft tumor model, WTAP knockdown not only alleviated CD8⁺ T cell exhaustion and inhibited tumor progression but also synergistically enhanced the antitumor efficacy of anti-PD1 therapy. In conclusion, WTAP promoted CD8⁺ T cell exhaustion and HCC progression by facilitating the m6A modification and translation of PD1 mRNA.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6217272"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497472","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":"Inflammatory Markers Mediate the Association Between Cardiovascular Health and Chronic Inflammatory Airway Diseases: A Cross-Sectional Study on the Population Aged 50 Years and Above From NHANES 2013-2018.","authors":"Zhaoqi Yan, Xiufan Du, Jing Zhang","doi":"10.1155/mi/2128440","DOIUrl":"10.1155/mi/2128440","url":null,"abstract":"<p><p><b>Objective:</b> This cross-sectional study collected data from participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018, aiming to investigate the association between cardiovascular health (CVH) and chronic inflammatory airway diseases (CIADs). <b>Methods:</b> Single-factor and multiple-factor logistic regression analyses were used to explore the relationship between CVH levels assessed based on Life's Essential 8 (LE8) scores and CIAD. Subgroup and interaction analyses were conducted and restricted cubic splines (RCSs) were used to evaluate the linear or nonlinear relationship between LE8 scores and CIAD. Mediation analysis was conducted to investigate the mediating role of inflammatory markers between CVH levels and CIAD. <b>Results:</b> A total of 5736 participants were included in this study. When participants with high CVH levels (LE8 scores: 80-100) were used as the reference standard, the average risk of CIAD increased by 1.78 times in participants with moderate CVH (odds ratio (OR) = 1.78, 95% confidence interval (CI) (1.25, 2.51)) and the risk of CIAD in participants with low CVH increased by 2.45 times (OR = 2.45, 95% CI (1.53, 3.94)). Subgroup analysis indicates that older age and comorbidities are significantly associated with CIAD and there is no interaction between various covariates and CVH levels. RCS showed a negative linear relationship between LE8 scores and CIAD. Mediation analysis results revealed that neutrophil (NEU) count and Systemic Immune-Inflammation (SII) Index significantly mediated the relationship between CVH and CIAD. <b>Conclusion:</b> Moderate and low levels of CVH pose a threat for developing CIAD, with inflammatory factors playing a major mediating role in this association.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2128440"},"PeriodicalIF":4.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475756","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":"Immune Regulation and ECM-Related Pathway Enrichment Reveal ATP2A3 as a Prognostic Biomarker for Nonspecific Orbital Inflammation: An Integrated Machine Learning and Mendelian Randomization Analysis.","authors":"Zixuan Wu, Xi Long, Kang Tan, Xiaolei Yao, Qinghua Peng","doi":"10.1155/mi/7061507","DOIUrl":"10.1155/mi/7061507","url":null,"abstract":"<p><p><b>Background:</b> Nonspecific orbital inflammation (NSOI) is a heterogeneous inflammatory disorder of the orbit with an unclear etiology. ATP2A3, a key regulator of calcium homeostasis in the endoplasmic reticulum (ER), may play a pivotal role in NSOI pathogenesis. Its potential as a diagnostic biomarker merits thorough investigation. <b>Methods:</b> Differentially expressed genes (DEGs) common to two GEO datasets (GSE58331 and GSE105149) were intersected with immune-related genes from the ImmPort database, yielding 89 candidates. ATP2A3 was prioritized using machine learning (ML) approaches, including LASSO, support vector machine (SVM)-RFE, and weighted gene coexpression network analysis (WGCNA). Functional enrichment was assessed using GSEA and GSVA based on genes co-expressed with ATP2A3. Immune microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE. Expression of ATP2A3 was validated in GSE105149. <b>Results:</b> Fifteen hub genes were identified, with ATP2A3 strongly linked to immune-related pathways. Genes positively correlated with ATP2A3 were enriched in sensory perception and extracellular matrix (ECM) organization. Immune infiltration analysis revealed a positive association between ATP2A3 expression and memory B cells, M2 macrophages, resting mast cells, monocytes, and regulatory T cells (Tregs), while naive B cells and plasma cells were negatively associated. ATP2A3 exhibited significant diagnostic potential for distinguishing NSOI. <b>Conclusions:</b> In the context of NSOI, we identify ATP2A3 as a novel contributor to immune-driven pathogenesis. Its significant dysregulation in NSOI tissues relative to healthy controls underscores its potential as a prognostic marker within the inflammatory microenvironment.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7061507"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475755","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}