Journal of Inflammation Research最新文献

{"title":"Causal Association Between Genetically Predicted Circulating Metabolites and Pressure Ulcers: A Two-Sample Mendelian Randomization Study.","authors":"Xiaoli Hu, Yue Zhang, Yuchao Wu, Miao Peng","doi":"10.2147/JIR.S503370","DOIUrl":"10.2147/JIR.S503370","url":null,"abstract":"<p><strong>Introduction: </strong>Pressure ulcers (PU) are skin and soft tissue injuries caused by prolonged localized pressure, friction, or shear forces, particularly affecting individuals with limited mobility. Understanding the mechanisms behind PU formation, including the role of metabolites, is crucial for effective prevention.</p><p><strong>Methods: </strong>We conducted a two-sample MR analysis to explore the causal relationship between circulating metabolites and PU. Exposure data included GWAS data for 1400 metabolites, while outcome data were sourced from a Finnish database. We used multiple MR methods (IVW, MR-Egger, WM, Simple mode, Weighted mode) to estimate causal effects and performed sensitivity analyses to assess robustness. Additionally, we validated the effects of key metabolites on PU through animal experiments.</p><p><strong>Results: </strong>A total of 19 metabolites demonstrated significant causal associations with PU (P < 0.01). Among them, 7 metabolites were linked to PU increased risk, the highest ORs was (IVW: OR [95% CI] = 1.3690 [1.0852-1.7270]; P = 0.0080) for the spermidine to choline ratio. 12 metabolites with positive effects on PU prevention, the homostachydrine levels showing a highest association (IVW: OR [95% CI] = 0.7497 [0.6206-0.9056]; P = 0.0028). Sensitivity analyses supported these findings and validated the stability of the results. In animal experiments, rats treated with HD-Hom and LR (Spe/Cho) showed the fastest scab shedding and new epithelial tissue formation, with the smallest residual wound area.</p><p><strong>Conclusion: </strong>This study highlights significant causal relationships between circulating metabolites and PU risk. The identification of the spermidine to choline ratio as a risk factor and homostachydrine levels as a protective factor suggests potential metabolic targets for PU prevention and treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6907-6926"},"PeriodicalIF":4.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208717","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":"Single-Cell Analysis Reveals Aspirin Restores Intervertebral Disc Integrity via Ferroptosis Regulation.","authors":"Haiyun Niu, Hao Qi, Peng Zhang, Hongyu Meng, Ning Liu, Di Zhang","doi":"10.2147/JIR.S519218","DOIUrl":"10.2147/JIR.S519218","url":null,"abstract":"<p><strong>Background: </strong>Low back pain represents a major global health issue, with intervertebral disc degeneration (IVDD) being one of its primary causes. Disc degeneration involves complex processes such as inflammation, matrix degradation, and cell death, yet the underlying mechanisms remain poorly understood. Single-cell RNA sequencing offers a powerful approach to elucidate cellular heterogeneity and dynamic changes in IVDD, providing valuable insights for early diagnosis and targeted therapeutic strategies.</p><p><strong>Methods: </strong>The Harmony algorithm was used to integrate four independent single-cell sequencing datasets. Subtype identification, differential expression analysis, enrichment analysis, and cell proportion analysis were conducted to explore functional alterations in various nucleus pulposus cell (NPC) subpopulations. Molecular docking was employed to evaluate the stability of aspirin targeting GPX4. In vitro and in vivo experiments were performed to assess the therapeutic effects of aspirin on IVDD.</p><p><strong>Results: </strong>Eight distinct NPC subtypes were identified based on cellular heterogeneity and their associated marker genes. The CDKN1A⁺aNPC subtype increased progressively with disease severity, while the matrix-supporting ABI3BP⁺mNPC and SOD3⁺mNPC subtypes significantly decreased in advanced degeneration. Concurrently, there was an increase in ECM remodeling-related LTBP1⁺mNPCs. Within the CDKN1A⁺aNPC, GPX4 was notably downregulated, suggesting the activation of ferroptosis. Molecular docking results revealed a high affinity of aspirin for GPX4. Additionally, aspirin inhibited ferroptosis and ameliorated disc structural damage.</p><p><strong>Conclusion: </strong>The increased proportion of CDKN1A⁺aNPC cells serves as an early warning feature for the progression of IVDD. Aspirin stabilizes the targeting of GPX4, thereby inhibiting ferroptosis and exerting therapeutic effects on IVDD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6889-6905"},"PeriodicalIF":4.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199386","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":"A Simplified Immune-Dysregulation Index (IL-6/LY) as a Robust Predictor of 28-Day In-Hospital Mortality and MODS in Patients with Sepsis.","authors":"Meili Liu, Tao You, Shifeng Li, Yan Hao, Zhiyang Wang, Fang Huang, Jun Wang","doi":"10.2147/JIR.S521684","DOIUrl":"10.2147/JIR.S521684","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the prognosis significance of a newly simplified immune-dysregulation index, interleukin-6-to-lymphocyte ratio (IL-6/LY), in individuals diagnosed with sepsis.</p><p><strong>Methods: </strong>This was a retrospective cohort study enrolling consecutive patients diagnosed with sepsis who qualified the inclusion criteria and were admitted to the intensive care unit of the First Affiliated Hospital of Soochow University between March 2017 and January 2023. Multivariate COX and logistic regression models were used to estimate the association between IL-6/LY and 28-day in-hospital mortality or multiple organ dysfunction syndrome (MODS). Restricted cubic splines and survival analysis were used to show a nonlinear correlation between IL-6/LY and mortality. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognostic value of IL-6/LY. was performed using the Kaplan‒Meier method.</p><p><strong>Results: </strong>The study encompassed 301 participants, categorized into two groups-those with low IL-6/LY and high IL-6/LY-determined by the cutoff value of 326.04. On multivariate analyses, a high IL-6/LY was independently associated with 28-day in-hospital mortality (hazard ratio [HR]: 8.01, 95% confidence interval [CI] 4.67-13.74, <i>P</i> < 0.001) and MODS (odds ratio [OR] 3.44, 95% CI 1.85‒6.38, <i>P</i> < 0.001). The area under the curve of IL-6/LY for predicting death and MODS were 0.893 (95% CI, 0.855-0.931) and 0.743 (95% CI, 0.688-0.798), respectively. The Kaplan‒Meier analysis showed a significantly higher risk of mortality in the high IL-6/LY group (≥ 326.04) (log-rank <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>The IL-6/LY is significantly associated with the risk of 28-day in-hospital mortality and MODS in patients with sepsis, making it a potential prognostic marker for risk stratification, which enables early identification of high-risk patients, timely interventions, and personalized treatment strategies to optimize patient outcomes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6945-6958"},"PeriodicalIF":4.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199374","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":"METTL16 Contributes to Coronary Heart Disease by Inducing TET2 m6A Modification.","authors":"Renjie Ruan, Yunrui Zhang","doi":"10.2147/JIR.S487828","DOIUrl":"10.2147/JIR.S487828","url":null,"abstract":"<p><strong>Background: </strong>Coronary heart disease (CHD) ranks as the primary cause of global morbidity and mortality. Despite of the progress in exploring risk factors and developing medications, considerable residual risk persists. In recent years, epigenetic regulation has emerged as a critical regulatory mechanism across various diseases. This study aimed to investigate the effects of methyltransferase-like protein 16 (METTL16) on CHD and the potential molecular mechanisms.</p><p><strong>Methods: </strong>A CHD mouse model was established and treated with METTL16 depletion treatment. The METTL16 RNA level was measured by qPCR assay. Cardiac function was estimated by using echocardiography. Tissue damage and cardiac fibrosis were analyzed by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Masson's trichrome staining. The blood samples were collected to measure lipid levels and cardiac function biomarkers. Vascular smooth muscle cells (VSMCs) were isolated, and cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation assay. Cell apoptosis was determined by flow cytometry. Expression of apoptosis biomarkers was detected by Western blotting assay. The m6A enrichment on TET2 mRNA was determined by methylated RNA immunoprecipitation (MeRIP) assay and cross-Linking Immunoprecipitation and qPCR (CLIP-qPCR).</p><p><strong>Results: </strong>We observed elevated expression of METTL16 in cardiac tissues of CHD mice, and knockdown of METTL16 notably recovered the cardiac function, alleviated cardiac fibrosis, and decreased lipid levels. Knockdown of METTL16 suppressed VSMC proliferation and elevated cell apoptosis. METTL16 directly modulated the m6A enrichment on TET2 mRNA, and overexpression of TET2 could reverse the inhibitory effects of siMETTL16 on VSMC proliferation.</p><p><strong>Conclusion: </strong>METTL16 affects the cardiac damage and function during CHD via epigenetically modulating the m6A modification of TET2.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6821-6830"},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199381","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 Insights into the Regulatory Role of N6-Methyladenosine in the Pathogenesis and Clinical Treatment of Osteoarthritis: Research Status and Prospect.","authors":"Mingyu He, Jian Liu, Yanqiu Sun, Yanyan Fang, Fanfan Wang","doi":"10.2147/JIR.S508973","DOIUrl":"10.2147/JIR.S508973","url":null,"abstract":"<p><p>Osteoarthritis (OA) is caused by characteristic joint tissue lesions characterized by chronic joint pain, stiffness, and limited mobility. OA is one of the most common causes of chronic disability in adults, seriously affecting the quality of life of patients and causing huge medical and socio-economic burdens. N6-methyladenosine (m6A) is a methylation that occurs at the N6 position of adenosine and is the most common chemical modification on eukaryotic RNA. m6A modification is a dynamic regulation process involving \"writers\" (methyltransferases), \"erasers\" (demethylases), and \"readers\" (reading proteins). Disruption or interference of this dynamic modification may lead to dysregulation of cellular regulatory mechanisms, resulting in various diseases. This article summarized the regulatory mechanism of m6A modification in OA pathogenesis, including regulation of inflammatory response and immune infiltration, extracellular matrix (ECM) degradation, programmed cell death, bone homeostasis, and osteogenic differentiation. Finally, the application and future development prospects of m6A modification in the clinical treatment of OA were further discussed.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6749-6766"},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199384","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":"Early Elevation of Monocytic-to-Polymorphonuclear Myeloid-Derived Suppressor Cells Ratio in Critical Illness is Associated with Favorable Clinical Outcomes.","authors":"Lijing Jia, Ling Long, Huawei Wang, Chen Ge, Ze Zhang, Zhiyang Zhang, Heling Zhao","doi":"10.2147/JIR.S517333","DOIUrl":"10.2147/JIR.S517333","url":null,"abstract":"<p><strong>Background: </strong>Myeloid-derived suppressor cells (MDSCs), comprising polymorphonuclear (PMN-MDSCs) and monocytic subsets (M-MDSCs), are immunosuppressive immature myeloid cells implicated in disease progression and prognosis across multiple pathologies.</p><p><strong>Purpose: </strong>To investigate the clinical significance of early MDSCs subset expansion in critical illness and identify novel prognostic biomarkers for risk stratification.</p><p><strong>Patients and methods: </strong>This prospective study enrolled 85 critically ill adults (APACHE II ≥15), stratified into survivors (n=47) and non-survivors (n=38). MDSCs subsets were quantified via flow cytometry. Concurrent measurements included lactate, IL-6, CRP, lymphocyte subsets, and Tregs. Primary outcomes were 28-day all-cause mortality and secondary infection rates.</p><p><strong>Results: </strong>Survivors exhibited significantly higher M-MDSCs% (median [IQR]: 4.824 [1.863-9.776] vs 2.503 [1.480-5.224], P<0.05) and elevated M-MDSCs/PMN-MDSCs ratios (122.166 [34.220-307.500] vs 28.324 [5.042-88.128], P<0.01). Patients with M-MDSCs/PMN-MDSCs ratios ≥85.765 demonstrated markedly lower mortality (23.08% vs 59.19%; hazard ratio [HR] = 3.530, 95% confidence interval [CI]: 1.668-7.467, P<0.001), with the low-ratio group exhibiting a 2.56-fold higher mortality risk. A combined stratification model (M-MDSCs/PMN-MDSCs + APACHE II score) revealed a 7.48-fold increase in mortality in the low-ratio/high-APACHE II subgroup compared to the high-ratio/low-APACHE II subgroup (86.36% vs 11.54%, P<0.001).</p><p><strong>Conclusion: </strong>Elevated levels of M-MDSCs in the early stages of critical illness may exert protective effects. The ratio of M-MDSCs/PMN-MDSCs demonstrates predictive value for 28-day mortality, positioning it as a potential biomarker for prognostic assessment, but further multicenter studies are still needed to validate it.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6807-6819"},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199376","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":"Expression and Clinical Significance of IL-33 and IL-25 in Post-Irradiation Otitis Media with Effusion.","authors":"Zhihe Lin, Chuntao Deng, Dan Wang, Bo Lyu, Jiaying Pan, Jinlian Li, Minting Chen, Zhaoxia Zhang, Zibin Liang, Lei Chen, Shaoyan Feng","doi":"10.2147/JIR.S507516","DOIUrl":"10.2147/JIR.S507516","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates IL-33 and IL-25 expression in post-radiation otitis media with effusion (POME), along with classic oxidative stress markers (MDA and SOD), to investigate radiation-induced oxidative stress and its association with ILC2-mediated chronic inflammation, providing basis for targeted therapies.</p><p><strong>Methods: </strong>Middle ear effusions (MEE) were collected from 35 irradiated nasopharyngeal carcinoma patients with otitis media with effusion (POME, 43 ears) and 20 non-irradiated conventional chronic otitis media with effusion (CCOME, 20 ears) patients. IL-33, IL-25, IL-6, SOD, and MDA levels were measured by ELISA. Eustachian tube function was evaluated using the Endoscopic Evaluation of the Eustachian Tube (3ET) scoring system.</p><p><strong>Results: </strong>Comparative analysis revealed distinct molecular profiles between POME and CCOME, with POME showing significantly reduced IL-33 levels (p=0.046) but elevated SOD activity (p=0.015), along with a non-significant trend toward higher MDA (p=0.083). Temporal analysis demonstrated peak expression of both IL-25 and IL-33 at 6 months post-radiation. Correlation studies identified significant associations between IL-33 (r=0.391) and IL-6, as well as between IL-25 (r=0.483) and IL-6 (both p<0.01). Clinically, IL-25 levels showed positive correlation with 3ET endoscopic scores (r=0.407, p=0.021) and were significantly reduced following tympanostomy tube placement (p=0.024). Notably, no direct correlation was observed between IL-33 and IL-25 (p>0.05), nor were any significant associations found with allergic comorbidities (all p>0.05).</p><p><strong>Conclusion: </strong>IL-33 and IL-25 synergistically drive ILC2-mediated chronic inflammation in radiation-induced OME, with IL-25 emerging as a biomarker for radiotherapy-associated Eustachian tube dysfunction. The 6-month cytokine surge post-radiation highlights a therapeutic window for targeted interventions to mitigate long-term complications.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6877-6887"},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199377","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":"Integrated Early CRP Kinetics and Plasma EBV DNA Clearance as Prognostic Biomarkers in De Novo Metastatic Nasopharyngeal Carcinoma Treated with First-Line Chemoimmunotherapy.","authors":"Min Fang, Yujun Hu, Tiejun Wang, Yong Su, Tianzhu Lu, Hao Zhang, Jingao Li, Chuanmiao Xie, Xiaochang Gong","doi":"10.2147/JIR.S512808","DOIUrl":"10.2147/JIR.S512808","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the predictive value of early C-reactive protein (CRP) kinetics in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving first-line chemotherapy combined with anti-PD-1 mAbs (first-line chemoimmunotherapy).</p><p><strong>Patients and methods: </strong>Patients were categorized into three groups based on early CRP kinetics within one and three months after the start of immunotherapy: (1) CRP flare-responders, with CRP levels rising to more than double the baseline within one month and subsequently falling below baseline within three months; (2) CRP non-flare-responders, with CRP levels decreasing by more than 30% within three months without initial flare; (3) CRP non-responders, with no significant CRP changes. Associations with objective response rate (ORR), and progression-free survival (PFS) were evaluated.</p><p><strong>Results: </strong>The multicenter study included 149 patients with dmNPC (median follow-up: 22 months). The cohort comprised 39 (26.2%) CRP flare-responders, 76 (51%) CRP non-flare-responders, and 34 (22.8%) CRP non-responders. CRP flare-responders and non-flare-responders were combined into CRP responders, showing significantly improved ORR (94.8% vs 79.4%, P=0.009) and prolonged median PFS (20 vs 13 months, P=0.006) compared to CRP non-responders. Multivariable analysis identified early CRP kinetics as an independent prognostic factor for PFS (HR=2.688, 95% CI: 1.484-4.868, P<0.001). In subgroup analysis, patients with undetectable EBV DNA after three immunotherapy cycles showed higher median PFS among CRP responders compared to non-responders (28 vs 21 months, P=0.014), whereas no significant difference was observed in patients with detectable EBV DNA levels (13 vs 8 months, P=0.142).</p><p><strong>Conclusion: </strong>CRP responders are associated with improved survival outcomes, particularly in patients achieving early EBV DNA clearance. Early CRP kinetics combined with early plasma EBV DNA clearance may be predictive of survival outcomes in dmNPC patients receiving first-line chemoimmunotherapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6783-6794"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199379","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":"Mitophagy-Related Gene CHDH Predicts Prognosis and Immune Response and Inhibits Proliferation and Migration in vitro and in vivo of Oral Squamous Cell Carcinoma.","authors":"Lingke Chen, Zheng Zhou, Lian Guo, Zhongrun He, Wen Luo, Ying Fu, Qiyu Xiao, Bo Liu, Pengxin Huang","doi":"10.2147/JIR.S516427","DOIUrl":"10.2147/JIR.S516427","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Mitophagy is a special type of cellular autophagy that plays an important role in tumors, but its role in OSCC is still unclear.</p><p><strong>Methods: </strong>Mitophagy-related genes (MRGs) were obtained from the GeneCards database. Differential expression analysis was used to identify differentially expressed genes (DEGs) in tumor samples and normal samples. Univariate Cox regression was then performed on the DEGs to determine prognostic MRGs, which were used to compare CNV mutation frequencies and construct consensus cluster analysis. Risk models were constructed to evaluate the prognosis and immune status of OSCC patients. Univariate and multivariate Cox regression analyses were performed to determine MRGs that independently predicted OSCC prognosis. The expression levels of genes and their effects on OSCC proliferation, migration, and invasion were further validated by in vitro and in vivo studies.</p><p><strong>Results: </strong>We identified 298 DEGs associated with OSCC survival, and 8 genes were used to create a risk model that can accurately predict the prognosis of OSCC patients, which can accurately assess the immune status of patients with different risks. OSCC patients were clustered into 2 subtypes, and there were significant differences between the two subtypes. Drug sensitivity analysis was used to select 72 sensitive drugs for the low-risk group and 9 sensitive drugs for the high-risk group. Choline dehydrogenase (CHDH) was identified as a reliable and independent predictor of OSCC. CHDH overexpression significantly inhibited OSCC cell proliferation, migration, colony formation, and tumor growth.</p><p><strong>Conclusion: </strong>This study's prediction model, created using MRGs, may accurately predict the prognosis and immune response of patients with OSCC. CHDH is essential to the development and progression of OSCC and can be a potential target for treating OSCC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6831-6851"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199382","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":"Chronic Inflammation Index-Based Tumor Subsite Classification Correlated with Chemotherapy Benefit and Survival Outcomes in Stage II-III Colorectal Cancer.","authors":"Ying Lu, Qiu-Ying Ye, Ou Mei, Ya-Nan Li, Yue Peng, Hou-Qun Ying, Xue-Xin Cheng","doi":"10.2147/JIR.S517378","DOIUrl":"10.2147/JIR.S517378","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop and validate an integrated inflammatory prognostic index and to investigate associations between primary tumor location, chronic inflammatory status, adjuvant chemotherapy response, and survival outcomes in stage II-III colorectal cancer (CRC).</p><p><strong>Patients and methods: </strong>A total of 1413 stage II-III CRC patients who underwent radical resection were enrolled and divided into discovery and validation cohorts. Preoperative systemic inflammatory biomarkers were quantified, and patients were followed for 3 years to establish an optimal chronic inflammatory index (CII) and evaluate its association with survival and chemotherapy efficacy across primary tumor locations.</p><p><strong>Results: </strong>The comprehensive CII was the top-performing prognostic biomarker, with time-dependent AUCs of 0.71(95% CI: 0.68-0.74) for 36-month RFS and 0.74(95% CI: 0.70-0.77) for OS. Furthermore, the 3C (CII, CEA and CA19-9) combined score demonstrated prognostic predictive AUCs of 0.74(95% CI: 0.71-0.77) for RFS and 0.76(95% CI: 0.72-0.79) for OS in the overall population. The splenic flexure and ascending colon showed significantly elevated CII levels versus other subsites, and the disease was divided into the proximal colon, transverse colon, distal colon and rectum. A significant CII gradient emerged across subsites (proximal > transverse > distal > rectal), with corresponding survival decrements (log-rank <i>p</i> < 0.001). Proximal CRC exhibited marked worse survival outcomes (<i>p</i> = 0.002 for RFS and <i>p</i> = 0.001 for OS) and inferior chemotherapy efficacy (<i>p</i> < 0.001 for RFS and OS) versus rectal cancer, with no significant differences between adjacent subsites (all <i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>The validated CII represents a biologically relevant, subsite-specific prognostic biomarker in CRC. The chronic inflammation-based tumor subsite classification correlated with chemotherapy efficacy and clinical outcomes, highlighting its potential for personalized treatment strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"6767-6781"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199375","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}