Mediators of Inflammation最新文献

{"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":"https://doi.org/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":"https://doi.org/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}

{"title":"Bone Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Articular Cartilage Through Regulating tRF-Gln-TTG-019/UBL3.","authors":"Xialin Li, Zheng Huang, Min Shu, Guangxun Hu, Weihong Yi, Yang Duan, Songjia Ni","doi":"10.1155/mi/2705953","DOIUrl":"https://doi.org/10.1155/mi/2705953","url":null,"abstract":"<p><p>The tRNA-derived fragments (tRFs) are newly discovered noncoding RNAs enriched in extracellular vesicles (EVs). However, the effects of tRFs as biomarkers have not been investigated in cartilage repair. Bone mesenchymal stromal cells (BMSCs) were isolated from male Sprague Dawley (SD) rats, and high-throughput sequencing was used to select tRFs from EVs derived from BMSC which were cultured in chondrogenic induction medium (induced) or stem cell growth medium (control). We established the rat cartilage defect model of the knee joint, in which physiological changes were examined by immunohistochemistry (IHC), to test the protective effect of BMSC-derived EVs and tRF-related molecules. Primary chondrocytes from rat knee joint treated with oxygen-glucose deprivation/reperfusion (OGD/R) were used to investigate the effect of related EVs and tRF on cell proliferation and apoptosis. BMSC-derived EVs could repair the defected cartilage of rat knee joint. OGD/R significantly reduced chondrocytes proliferation, induced chondrocyte apoptosis and inflammation, while BMSC-derived EVs reversed these effects. Additionally, tRF-Gln-TTG-019 significantly increased in EVs derived from differentiated BMSCs when compared with control group. Knockdown ubiquitin-like 3 (UBL3, a molecular target of tRF-Gln-TTG-019) inhibited chondrocytes apoptosis and inflammation induced by OGD/R, and this effect could be synergistically enhanced when co-cultured with BMSC-EVs, but the protection was partly reversed by tRF-Gln-TTG-019 inhibitor. Then we further validated that suppression of UBL3 could promote the proliferation of chondrocytes, inhibit inflammation, and enhance the repair ability of cartilage tissue in a rat cartilage defect model. Similarly to the previous results, BMSC-derived EVs could synergistically enhance these effects, while tRF-Gln-TTG-019 inhibitor weakened them. Our results indicate that tRF in BMSC-derived EVs modulates the process of cartilage repair by regulating UBL3.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2705953"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475753","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":"CCL2 Inhibitor Bindarit Improve Postoperative Cognitive Function by Attenuating Pericyte Loss-Related Blood-Brain Barrier Disruption and Neuroinflammation.","authors":"Hui Yuan, Bo Lu, Daofan Sun, Junping Chen, Xiangming Fang","doi":"10.1155/mi/7248780","DOIUrl":"https://doi.org/10.1155/mi/7248780","url":null,"abstract":"<p><p>Perioperative neurocognitive disorder (PND) is a common complication in elderly patients undergoing surgery and anesthesia and associated with the impaired recovery. Previous studies have demonstrated that PND was correlated with the pericyte (PC) loss in brain, but the underlying mechanisms remain unclear. This study investigates whether C-C motif chemokine ligand 2 (CCL2) in hippocampal tissues contributes to postoperative PC injury, blood-brain barrier (BBB) disruption, neuroinflammation, and cognitive dysfunction. Sixteen-month-old C57BL/6 mice underwent tibial fracture surgery to induce PND. CCL2 expression in hippocampal tissues was downregulated using intraperitoneal injections of 200 mg/kg daily Bindarit for 4 days prior to surgery. Behavioral tests were conducted on the third day postsurgery and brain tissues were collected. Western blotting assessed CCL2 expression in the hippocampus, immunofluorescence evaluated PC coverage, BBB integrity, and neuroinflammation, and transmission electron microscopy (TEM) examined BBB microstructure. Bindarit effectively inhibited the surgery-induced increase in hippocampal CCL2 expression and improved postoperative cognitive function. Behavioral tests, including the open field (OF) test and novel object recognition (NOR) test, indicated enhanced locomotor activity and short-term memory in Bindarit-treated mice compared to controls. Immunofluorescence analysis revealed that Bindarit treatment mitigated the reduction in capillary length and tight junction (TJ) protein expression, specifically claudin-5 and occludin, which was seen with decreased PC coverage. Additionally, Bindarit suppressed the activation of hippocampal microglia and astrocytes, as evidenced by reduced Iba-1 and GFAP staining. TEM analysis confirmed that Bindarit preserved BBB microstructure integrity postsurgery. This study demonstrates that the CCL2 inhibitor Bindarit significantly reduces the incidence of PND by preventing PC loss, thereby protecting the BBB and alleviating neuroinflammation. These findings suggest that targeting CCL2 could be a potential therapeutic strategy for preventing and treating PND.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7248780"},"PeriodicalIF":4.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475754","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":"S100A11 Promotes Acute Pancreatitis by Upregulating Acinar Cell Ferroptosis.","authors":"Huiyun Zhu, Hongxin Sun, Xianzhu Zhou, Ge Li, Yun Zhang, Youhan Zhang, Jia Gui, Siying Fei, Xiaoyang Dong, Xiaoju Su, Yan Chen, Cui Chen, Yiqi Du","doi":"10.1155/mi/6971024","DOIUrl":"10.1155/mi/6971024","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common gastrointestinal disease that can cause systemic inflammation and lead to dysfunction of multiple organs. In pancreatitis, ferroptosis promotes disease progression and organ damage by regulating oxidative stress and inflammatory response. Here, ferroptosis was significantly elevated in the AP rat model and participated in regulating disease progression. Meanwhile, the expression of S100A11 was significantly upregulated in the pancreatic tissue of rats with AP, as determined by tandem mass spectrometry (TMT) proteomics. This phenomenon was also confirmed in pancreatic acinar cells. To reveal whether S100A11 participates in regulating ferroptosis, an S100A11 knockdown lentivirus was transfected into caerulein-treated pancreatic acinar cells AR42J. Functional results revealed that S100A11 knockdown significantly increased cell viability and GSH levels, while decreasing reactive oxygen species (ROS), lipid ROS, and Fe²⁺ levels in pancreatic acinar cells compared to the control group. In vivo, S100A11 knockdown via adeno-associated virus inhibited caerulein-induced ferroptosis. These findings suggest that S100A11 promotes AP by upregulating ferroptosis, which exacerbates oxidative stress and inflammation in pancreatic tissue.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6971024"},"PeriodicalIF":4.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333455","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":"Investigation of the Renal Defensive Influence of Walnut Septa Extract Against Acute Renal Ischemia/Reperfusion Injury.","authors":"Seda Askin, Khasiiat Iminova, Bahri Avci, Hakan Askin","doi":"10.1155/mi/9713697","DOIUrl":"10.1155/mi/9713697","url":null,"abstract":"<p><p><b>Aim:</b> Acute kidney injury (AKI), also known as renal failure among the public, is the sudden decrease or loss of kidney functions. In the treatment of this condition, drugs with anti-inflammatory properties are generally preferred, but these drugs have many side effects. Physicians may need natural antioxidants as an alternative or additional treatment to the applied treatment to eliminate or reduce these side effects. Therefore, we conducted our current study molecularly to reveal the protective potential of walnut septa extract (WSE) in targeting oxidative stress, inflammation, ferroptosis, and cellular differentiation mechanisms in kidney tissues in Sprague-Dawley rats with kidney damage. <b>Methods:</b> The bioactive compounds in this extract were identified. Before inducing a renal IR injury model in the rats this extract was administered. Then, tissue oxidative stress markers were detected by ELISA. Following the treatment, molecular analyses were performed to determine antioxidant, anti-inflammatory, ferroptosis, and cellular differentiation activities in kidney tissues. Gene expression levels of kidney injury molecule-1 (<i>Kim-1</i>), nuclear factor erythroid 2 (<i>Nrf2</i>), lipocalin 2 (<i>Lcn2</i>), glutathione (GSH) peroxidase 4 (<i>Gpx4</i>), and keratin 8 (<i>Krt8</i>) were assessed. <b>Results:</b> The primary bioactive compound identified in this extract was β-sitosterol, accounting for 62.066% of the total extract. Pretreatment with WSE led to an increase in GSH activity and a reduction in lactate dehydrogenase (LDH) levels in the kidney tissues. On a molecular level, this extract promoted the activation of <i>Gpx4</i>, <i>Krt8</i>, and <i>Nrf2</i> genes, while inhibiting the expression of <i>Kim-1</i> and <i>Lcn2</i> genes, indicating its protective effects. Extract was shown to exert renoprotective effects by reducing oxidative stress (<i>Gpx4</i> and <i>Nrf2</i>), suppressing inflammation (<i>Lcn2</i> and <i>Kim-1</i>), and supporting cellular structure and apoptosis regulation (<i>Krt8</i>). <b>Conclusion:</b> These findings suggest that extract could be a promising therapeutic candidate for renal ischemia-reperfusion (RIR) injury. Further comprehensive and long-term studies are recommended to validate these findings.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9713697"},"PeriodicalIF":4.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333454","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":"Temporal Effects of Disease Signature Genes and Core Mechanisms in the Hyperacute Phase of Acute Ischemic Stroke: A Bioinformatics Analysis and Experimental Validation.","authors":"Peng-Li Ding, Kai-Xin Zhang, Fang Yao, Wen-Qiang Cui, Zhen-Ling Liu, Yi-Ran Wang, Xiang-Ying Wang, Wei Liu, Heng-Ye Zhao, Hong-Yun Wu, Ya-Han Wang, Xiang-Qing Xu","doi":"10.1155/mi/6808184","DOIUrl":"10.1155/mi/6808184","url":null,"abstract":"<p><p><b>Background:</b> The pathophysiological progression during the hyperacute phase of acute ischemic stroke (AIS) critically determines clinical outcomes. Identification of phase-specific biomarkers and elucidation of their temporal regulatory mechanisms are pivotal for optimizing therapeutic interventions. <b>Methods:</b> Disease signature genes and their mechanisms of action were screened based on the Gene Expression Omnibus database. This involved the use of differentially expressed gene screening, weighted gene co-expression network analysis, Mfuzz analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, support vector machines, random forest algorithms, and gene set enrichment analysis. The expression of disease-characteristic genes and their related mechanisms were further validated in both in vivo and in vitro models. <b>Results:</b> Six hyperacute-phase signature genes (<i>Pip5k1c</i>, <i>Nlgn2</i>, <i>Fzd2</i>, <i>Cd86</i>, <i>Agpat1</i>, and <i>Degs2</i>) were identified in the hyperacute phase of AIS. In light of the gene effect mechanism, the regulation of the neuroinflammatory response and apoptosis by the TLR2/TLR4/NF-<i>κ</i>B pathway was monitored in the hyperacute phase of AIS at three times: 3, 6, and 12 h. The results indicated a progressively intensified neuroinflammatory response and the fluctuating growth of early apoptosis changes. <b>Conclusion:</b> This study systematically identifies hyperacute-phase-specific biomarkers in AIS and delineates their temporal regulatory logic. The time-course dynamics of neuronal apoptosis and inflammatory regulation in the hyperacute phase of AIS were monitored. The observed biphasic apoptotic pattern provides mechanistic insights for developing chronologically targeted therapies, such as timed inhibition of TLR4/CD86 during 0-3 h to block inflammatory initiation, or administration of Agpat1 agonists at 3-6 h to stabilize mitochondrial function. These findings help alleviate the current 'molecular blind spot' in early stroke diagnosis and intervention.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6808184"},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302485","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":"Gut Microbiota in Lactose Intolerance: A Mendelian Randomization Study on Microbial Mechanisms and Potential Links to Tumor Inflammatory Microenvironments.","authors":"Ya Xie, Qiongjiao Cao, Zhen Huang, Xin Zou","doi":"10.1155/mi/8181816","DOIUrl":"10.1155/mi/8181816","url":null,"abstract":"<p><p><b>Background:</b> Previous observational studies have suggested an association between the composition of the intestinal microbiome and lactose intolerance (LI). However, the causal direction remains unclear. This study utilized Mendelian randomization (MR) to rigorously evaluate the potential causal link between the gut microbiome and LI. <b>Methods:</b> Genome-wide association studies (GWASs) summary statistics for gut microbiota and LI were sourced from previously published GWAS studies. Multiple methods, such as Simple mode, MR-Egger regression, weighted median, inverse variance-weighted (IVW), and weighted model, were used to determine the causal relationship between gut microbiota and LI. To validate the primary findings from the MR analyses, several sensitivity analyses were conducted. Furthermore, a reverse MR analysis was executed on bacterial taxa previously identified to have a potential causal link with LI risk, aiming to evaluate the possibility of reverse causation. <b>Results:</b> The IVW results revealed that the genus <i>Lachnospiraceae UCG008</i> (OR = 0.584, 95%CI 0.356-0.958, <i>p</i>=0.0330), genus <i>Eubacterium hallii</i> group (OR = 0.467, 95% CI 0.242-0.899, <i>p</i>=0.023), and genus <i>Ruminococcus gauvreauii</i> group (OR = 0.506, 95% CI 0.2653-0.968, <i>p</i>=0.039) have a protective effect against LI. In contrast, the genus <i>Holdemania</i> (OR = 1.86, 95% CI 1.105-3.131, <i>p</i>=0.0194) displayed a predisposing effect. Sensitivity analyses did not detect any outlier single-nucleotide polymorphisms (SNPs). Further analyses reinforced the association between specific gut microbiota compositions and LI. No evidence suggested reverse causality between LI and the bacterial taxa identified in the reverse MR analysis. <b>Conclusions:</b> From a genetic standpoint, this MR study indicates a causal relationship between variations in gut microbiota composition and LI. This not only underscores the potential of gut microbiota-centric treatments for LI but also provides a foundation for exploring the role of gut microbiota in LI development. Further study of the mechanism of Lachnospiraceae in the treatment of IL is conducive to the discovery of new therapeutic targets for IL.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8181816"},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285399","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":"The Tumor-Associated Neutrophils-Related Signatures Predict Prognosis and Indicate Immune Landscape in Colorectal Carcinoma.","authors":"Ying Wang, Yizhen Zhu, Yuling Zeng, Shuhui Gao, Youcai Tang, Ming Wei","doi":"10.1155/mi/7259278","DOIUrl":"10.1155/mi/7259278","url":null,"abstract":"<p><p><b>Background:</b> Tumor-associated neutrophils (TANs), a major immune cell type in the tumor microenvironment (TME), are associated with antitumor or pro-tumor phenotypes. A wealth of evidence evidences demonstrated that the content of TANs has been implicated in the pathogenesis of cancer and may be ideal targets for cancer therapy. In this study, we identified TANs-related genes to construct a prognostic model and evaluated its potential as a biomarker for predicting prognosis and immunotherapeutic response in colorectal carcinoma (CRC). <b>Methods:</b> Kaplan-Meier survival curves were used to assess the impact of TANs infiltration on patient survival. Weighted Gene Co-Expression Network Analysis (WGCNA) identified genes associated with TANs. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression were applied to filter TANs-related risk signatures. A prognostic model was constructed using data from The Cancer Genome Atlas (TCGA) and validated with the GSE39582 dataset. Immune cell infiltration levels and immunotherapy responses were compared between high- and low-risk groups. Functional enrichment analysis was performed to identify relevant Gene Ontology (GO) terms and pathways. <b>Results:</b> Patients with elevated TANs levels have a low survival rate. Fourteen risk signature genes were identified, and a risk model was constructed based on these genes. Patients in the high-risk group had worse survival outcomes and improved responsiveness to immunotherapy. <b>Conclusions:</b> This study comprehensively analyzed the role of TANs in CRC progression and developed a prognostic model based on TANs-related genes, which holds significant potential for predicting prognosis and immunotherapy outcomes in CRC patients.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7259278"},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285402","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":"Integrative Analysis of Shared Pathogenic Genes and Potential Mechanisms in <i>Gardnerella vaginalis</i> and Persistent HPV16 Infection.","authors":"Ye Li, Yue Wang, Xianhua Liu, Huifeng Xue, Liying Wang, Maotong Zhang, Pengming Sun","doi":"10.1155/mi/2582989","DOIUrl":"10.1155/mi/2582989","url":null,"abstract":"<p><p>Bacterial vaginosis, often accompanied by <i>Gardnerella vaginalis</i> (GV) overgrowth, is associated with persistent high-risk human papillomavirus (HR-HPV) infection, particularly HPV16. This study integrated transcriptomic data from in vitro GV infection experiments and a GEO dataset (GSE75132) of HPV16 persistence to elucidate shared pathogenic mechanisms. Differential expression analysis identified 4115 genes modulated by GV infection and 861 by HPV16 persistence, with 74 common differentially expressed genes (DEGs) displaying consistent trends. Enrichment analyses revealed that these DEGs participate in metabolic pathways, immune defense, host-pathogen interactions, and carcinogenesis. Protein-protein interaction networks and Random Forest (RF) feature selection pinpointed radical S-adenosyl methionine domain containing 2 (RSAD2) and Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) as central hub genes. Upstream transcription analysis identified the homer_AGTTTCAGTTTC_ISRE motif and established a ceRNA network involving hsa-miR-654-5p, IFIT1/RSAD2, and lncRNAs. Mendelian randomization (MR) and colocalization analyses linked RSAD2 downregulation to an increased risk of cervical carcinoma in situ (rs2595163, PPH4 = 0.62), while ROC analysis demonstrated strong diagnostic potential for the combined hub gene expression. Notably, single-cell transcriptomics revealed distinct RSAD2 and IFIT1 expression patterns in immune and epithelial cells during the progression from HPV infection to cervical cancer. Collectively, these findings support RSAD2 and IFIT1 as promising biomarkers and therapeutic targets for HPV-related cervical lesions.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2582989"},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285401","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}