Journal of Inflammation Research最新文献

{"title":"Construction and Comparison of Multiple Serum-Based Prognostic Models for Predicting the Prognosis of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.","authors":"Na Wang, Guangdong Wang, Mengcong Li, Tingting Liu, Wenwen Ji, Tinghua Hu, Zhihong Shi","doi":"10.2147/JIR.S461961","DOIUrl":"https://doi.org/10.2147/JIR.S461961","url":null,"abstract":"<p><strong>Purpose: </strong>Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with significant poor prognosis. Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Eosinophil-to-Lymphocyte Ratio (ELR), Basophil-to-Lymphocyte Ratio (BLR), Platelet-to-Lymphocyte Ratio (PLR), and Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) are vital indicators for inflammation, immune status, and nutritional condition. This study evaluated the predictive value of these indicators in AECOPD and developed predictive models to assess the prognosis of AECOPD based on these indicators.</p><p><strong>Patients and methods: </strong>We retrospectively collected data from 2609 AECOPD patients. The outcomes assessed included occurrence of respiratory failure (RF), intensive care unit (ICU) stay, mechanical ventilation (MV), and 30-day readmission. We evaluated the predictive ability of LMR, NLR, PLR, BLR, ELR, and HALP for predicting the prognosis of AECOPD patients. Furthermore, based on these indicators, we utilized LASSO regression and multivariable analysis to develop models for predicting the prognosis of AECOPD patients. The predictive value of these indicators and the performance of the models were assessed using AUCs.</p><p><strong>Results: </strong>LMR exhibited AUCs of 0.612 for RF, 0.715 for ICU stay, 0.714 for MV, and 0.624 for 30-day readmission. Other indicators, including NLR, PLR, BLR, EMR, and HALP, showed AUCs ranging from 0.621 to 0.699 for predicting these outcomes in AECOPD. The models developed using LASSO regression and multivariable analysis yielded AUCs of 0.717 for RF, 0.773 for ICU stay, 0.780 for MV, and 0.682 for 30-day readmission. Incorporating LMR, NLR, PLR, BLR, ELR, and HALP into the models individually further enhanced predictive performance, particularly with LMR (AUCs of 0.753 for RF, 0.797 for ICU stay, 0.802 for MV, and 0.697 for 30-day readmission), NLR (AUCs of 0.753 for RF, 0.796 for ICU stay, 0.802 for MV, and 0.698 for 30-day readmission), and HALP (AUCs of 0.752 for RF, 0.790 for ICU stay, 0.797 for MV, and 0.697 for 30-day readmission).</p><p><strong>Conclusion: </strong>Indicators of LMR, NLR, PLR, BLR, ELR, and HALP showed good performance in predicting outcomes for AECOPD patients. The integration of these indicators into prognostic models significantly enhances their predictive efficacy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8395-8406"},"PeriodicalIF":4.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622075","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":"Ferroptosis in Osteoarthritis: Current Understanding.","authors":"Yikai Liu, Zian Zhang, Yuan Fang, Chang Liu, Haining Zhang","doi":"10.2147/JIR.S493001","DOIUrl":"https://doi.org/10.2147/JIR.S493001","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent degenerative disease in elderly people that is characterized by cartilage loss and abrasion, leading to joint pain and dysfunction. The aetiology of OA is complicated and includes abnormal mechanical stress, a mild inflammatory environment, chondrocyte senescence and apoptosis, and changes in chondrocyte metabolism. Ferroptosis is a regulated cell death modality characterized by the excessive accumulation of lipid peroxidation and mitochondrial dysfunction. The role of ferroptosis in OA pathogenesis has aroused researchers' attention in the past two years, and there is mounting evidence indicating that ferroptosis is destructive. However, the impact of ferroptosis on OA and how the regulators of ferroptosis affect OA development are unclear. Here, we reviewed the current understanding of ferroptosis in OA pathogenesis and summarized several drugs and compounds targeting ferroptosis in OA treatment. The accumulation of intracellular iron, the trigger of Fenton reaction, the excessive production of ROS, the peroxidation of PUFA-PLs, and mitochondrial and membrane damage are involved in chondrocyte ferroptosis. System X_c ^- and GPX4 are the most important regulators that control ferroptosis. Several compounds, such as DFO and Fer-1, have been proven effective in preventing ferroptosis and slowing OA progression on animal models. Collectively, targeting ferroptosis shows great potential in treating OA.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8471-8486"},"PeriodicalIF":4.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622092","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":"CD200-CD200R Pathway: A Regulator of Microglial Polarization in Postoperative Cognitive Dysfunction.","authors":"Jie Sun, Daoyun Lei","doi":"10.2147/JIR.S489895","DOIUrl":"https://doi.org/10.2147/JIR.S489895","url":null,"abstract":"<p><p>Microglial polarization refers to the ability of microglia to exhibit different functional states under various conditions. As the resident immune cells of the brain, changes in the functional state of microglia play a crucial role in the progression of postoperative cognitive dysfunction. Recent studies have indicated that CD200-CD200R signaling is associated with microglial polarization. This review focuses on the latest advancements regarding whether CD200-CD200R signaling can regulate microglial polarization and thereby influence postoperative cognitive dysfunction.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8421-8427"},"PeriodicalIF":4.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622068","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":"Biological Roles and Clinical Therapeutic Applications of Tumor-Associated Macrophages in Colorectal Liver Metastasis.","authors":"Shenghao Li, Liyuan Hao, Xiaoyu Hu","doi":"10.2147/JIR.S493656","DOIUrl":"https://doi.org/10.2147/JIR.S493656","url":null,"abstract":"<p><p>Colorectal cancer (CRC) commonly metastasizes to the liver, and this poses a significant clinical challenge. Tumor-associated macrophages (TAMs), key players within the TME, play a significant role in promoting CRC metastasis by secreting various chemokines, growth factors, and cytokines. This review not only aims to enhance our knowledge of TAMs' functions in CRC progression and metastasis but also examines innovative therapeutic strategies to address the clinical problem of colorectal liver metastasis (CLM). By targeting TAMs, we may be able to develop more effective treatments and offer hope to patients suffering from this devastating disease.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8429-8443"},"PeriodicalIF":4.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622066","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 Nomogram-Based Prognostic Model for Lymphoma Patients Initially Presenting with Fever of Unknown Origin.","authors":"Lin Shen, Wenjing Young, Min Wu, Yanhui Xie","doi":"10.2147/JIR.S493158","DOIUrl":"https://doi.org/10.2147/JIR.S493158","url":null,"abstract":"<p><strong>Background: </strong>Patients with lymphoma who present with fever of unknown origin (FUO) as an initial symptom lack specific clinical feature analysis, prognostic factor analysis, and existing prognostic models. We aim to create a prognostic model for these patients to improve prognosis and risk assessment.</p><p><strong>Methods: </strong>A total of 555 lymphoma patients with FUO as initial symptom studied at Huadong Hospital affiliated with Fudan University. Univariable Cox regression identified outcome predictors, analyzed by LASSO Cox. Multifactorial Cox on screened coefficients determined independent prognostic factors and nomogram model. The validity of the nomogram was evaluated through bootstrap sampling, calibration curves for model calibration, time-dependent ROC curve analysis for discrimination assessment, and decision curve analysis for evaluating clinical usefulness. Further validation involved utilizing Kaplan-Meier curves and Log rank tests. Lastly, X-tile software determined the optimal cutoff point for the nomogram score by comparing it with the traditional International Prognostic Index (IPI) scoring system.</p><p><strong>Results: </strong>The entire cohort was divided into a training cohort (n=388) and a validation cohort (n=167). These risk factors (cell pathologic type, performance status score, Ann Arbor staging, thrombocytopenia, and raised direct bilirubin) were used to construct a web-based dynamic survival rate calculator for lymphoma patients initially presenting with FUO. The lymphoma-specific nomogram demonstrated good consistency and efficacy in predicting the model's risk stratification. Compared to the IPI scoring system, the nomogram model had higher AUC values for different clinical endpoints. The new nomogram prognostic model showed better differentiation of risk groups compared to traditional IPI scoring.</p><p><strong>Conclusion: </strong>Our study developed and validated a prognostic nomogram for lymphoma patients initially presenting with FUO, demonstrating robust predictive efficacy and risk stratification ability. Furthermore, we have successfully implemented this model into a web-based dynamic survival rate calculator.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8445-8469"},"PeriodicalIF":4.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622062","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":"Prognostic Value of Systemic Inflammation Response Index and N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries- A Retrospective Study.","authors":"Hua Hou, Yujia Xu, Guangxin Chen, Haifeng Yao, Fangjie Bi","doi":"10.2147/JIR.S482596","DOIUrl":"https://doi.org/10.2147/JIR.S482596","url":null,"abstract":"<p><strong>Background: </strong>The Systemic Inflammation Response Index (SIRI) and N-terminal Pro-B-type natriuretic peptide (NT-proBNP) have been proposed as reliable predictors of poor prognosis in cardiovascular disease and all-cause mortality, However, their validity has not been extensively evaluated in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA).</p><p><strong>Patients and methods: </strong>259 patients diagnosed with MINOCA were enrolled in this study from January 2015 to December 2022, and serum levels of SIRI and NT-proBNP were detected. The primary endpoints were major adverse cardiovascular events (MACE). According to the occurrence of MACE during the follow-up period, patients were grouped into MACE and Non-MACE groups, and divided by the median values for SIRI and NT-proBNP into groups: low SIRI, high SIRI, low NT-proBNP, and high NT-proBNP.</p><p><strong>Results: </strong>A statistically significant difference in the levels of SIRI and NT-proBNP was observed between the MACE group and the non-MACE group. Kaplan-Meier survival curve analysis revealed that patients with high SIRI and high NT-proBNP had a significantly higher risk of MACE (log-rank P < 0.001). Furthermore, even after adjusting for covariates, the high SIRI and high NT-proBNP were associated with an increased risk of MACE (P<0.001, HR: 3.188, 95% CI 1.940-5.241; P<0.001, HR: 2.245, 95% CI 1.432-3.519). Additionally, the combined prognosis prediction of SIRI and NT-proBNP was superior to a single prediction, and adding SIRI and NT-proBNP to the traditional risk factor model improved the model's predictive value.</p><p><strong>Conclusion: </strong>High levels of SIRI and NT-proBNP exhibit a significant correlation with an increased risk of MACE, thereby suggesting that SIRI can be used as a reliable inflammatory indicator for predicting the risk in MINOCA patients, with significantly improved prognostic value when combined with NT-proBNP.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8281-8298"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622121","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":"Sinulariolide Suppresses Inflammation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis and Mitigates Collagen-Induced Arthritis Symptoms in Mice.","authors":"Sen-Wei Tsai, Yu-Chieh Cheng, Ya-Hsuan Chao, Deng-Ho Yang","doi":"10.2147/JIR.S476847","DOIUrl":"https://doi.org/10.2147/JIR.S476847","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by active polyarthritis, which leads to functional loss and joint deformities. Natural compounds derived from marine organisms are considered valuable immune-modulating agents. This study aimed to assess the anti-inflammatory effect of sinulariolide, a soft coral-derived compound, on RA fibroblast-like synoviocytes and its therapeutic efficacy against collagen-induced arthritis (CIA).</p><p><strong>Methods: </strong>To determine the effects of sinulariolide on tumor necrosis factor-alpha (TNF-α)-induced inflammation, MH7A cells pre-treated with 10 ng/mL TNF-α for 24 h were treated with sinulariolide. The effect of sinulariolide on proinflammatory cytokine expressions at both the mRNA and protein levels in the MH7A cells was assessed using real-time-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Further, we analyzed the effect of sinulariolide on the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways using Western blotting and the TransAM NF-κB p65 kit. To comprehensively evaluate the potential application of sinulariolide in the treatment of inflammatory diseases, we used a well-established collagen-induced arthritis (CIA) mouse model. We examined the tissue sections of the ankle joints of the mice, assessed synovial hyperplasia, inflammatory cell infiltration, and cartilage damage, and used ELISA to analyze changes in cytokine expression in the hind paw tissues.</p><p><strong>Results: </strong>MH7A cells treated with sinulariolide showed a notable reduction in the expression of proinflammatory cytokines, which could be due to decreased activation of the MAPK and NF-kB pathways. Additionally, sinulariolide-treated mice showed significantly reduced joint swelling and lower clinical arthritis scores than those in the normal and control groups. Significant reductions in synovial hyperplasia, inflammatory cell infiltration, and cartilage damage were observed in the tissue sections of the ankle joints of the mice treated with sinulariolide. Furthermore, the expression of inflammatory cytokines in the hind paw tissue of the mice treated with sinulariolide was significantly decreased.</p><p><strong>Conclusion: </strong>Sinulariolide inhibited the progression of inflammation in MH7A cells. Sinulariolide treatment significantly reduced clinical arthritis symptoms and histological inflammatory responses in mice with CIA. Sinulariolide may serve as a potential therapeutic agent for RA.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8299-8311"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620624","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":"Relationship Between the Systemic Immune-Inflammation Index and Deep Venous Thrombosis After Spinal Cord Injury: A Cross-Sectional Study.","authors":"Fei Tian, Yuheng Lu, Xinyu Liu, Chenguang Zhao, Xiao Xi, Xu Hu, Yike Xue, Xiaolong Sun, Hua Yuan","doi":"10.2147/JIR.S491055","DOIUrl":"https://doi.org/10.2147/JIR.S491055","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the relationship between the systemic immune-inflammation index (SII) and deep venous thrombosis (DVT) in patients with spinal cord injury (SCI).</p><p><strong>Methods: </strong>This cross-sectional study included data from 382 participants with SCI. The SII was calculated for all participants. Logistic regression, smooth curve fitting, interaction effects were used to substantiate the research objectives.</p><p><strong>Results: </strong>The overall prevalence of DVT was 23.1% (22.4% among males, 25.6% among females). A positive association between SII and the risk for DVT was observed (odds ratio 1.39 [95% CI 1.03-1.87]; P=0.032), independent of confounders. Similar patterns of association were observed in the subgroup analysis (P values for interaction, all >0.05). Further sensitivity analyses provided confidence that the results were reliable and unlikely to be substantially altered by unmeasured confounding factors.</p><p><strong>Conclusion: </strong>Results of the present suggest that higher SII may be associated with DVT in patients with SCI, highlighting a potential link between SII and DVT. These findings underscore the potential of SII as a valuable predictive biomarker for DVT, thus offering a promising avenue for early detection and intervention strategies in patients with SCI.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8325-8334"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622081","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":"Exploring the Role of Inflammatory Genes and Immune Infiltration in Vestibular Schwannomas Pathogenesis.","authors":"Jinlu Gan, Yanling Zhang, Deqiang Lei, Yingchun Zhou, Hongyang Zhao, Lei Wang","doi":"10.2147/JIR.S476745","DOIUrl":"https://doi.org/10.2147/JIR.S476745","url":null,"abstract":"<p><strong>Background: </strong>Vestibular schwannomas (VSs) exhibit a range of tumor behaviors, such as growth patterns and auditory dysfunction. Recent research has offered insights into the inflammatory microenvironment in modulating tumor dynamics. This study investigates the role of inflammatory genes and immune infiltration in VS pathogenesis.</p><p><strong>Methods: </strong>We retrieved mRNA microarray data of VSs and normal nerves from the GEO database (GSE141801, GSE108524, and GSE56597), focusing on bioinformatic analysis of inflammatory response genes. Based on the evidence provided by bioinformatics analysis, we assessed the expression levels of Iba-1, IL-10, IL-10RA, and IL-18 in 31 VS patients via immunohistochemistry and delved into their association with tumor size and auditory dysfunction.</p><p><strong>Results: </strong>We identified 1117 differentially expressed genes (DEGs) in VSs compared to normal nerves, showing an upregulation in inflammatory pathways. Intersection with inflammatory response genes (IRG) yielded 41 significant IRG-DEGs. Network analysis identified a core module of 10 IRG-DEGs and 11 hub genes, most of which were inflammatory cytokines. Immune infiltration analysis showed macrophage activation and M2 polarization. These findings were validated in an independent dataset (GSE39645). To further explore the association between inflammation and tumor behaviors, immunohistochemistry analysis was conducted on VS samples and the results exhibited notable associations between the macrophage marker (Iba1) and inflammatory cytokines (IL-10, IL-10RA, and IL-18) with both tumor size and auditory dysfunction. In particular, the multiple regression analysis of inflammatory cytokines demonstrated that IL-10 and IL-10RA were statistically significant predictors of tumor size, while IL-18 was associated with hearing loss.</p><p><strong>Conclusion: </strong>Our study underscores the role of inflammation in VS pathogenesis, showing that macrophage activation with M2 polarization and the expression of inflammatory cytokines, especially IL-10/IL-10RA and IL-18, are linked to tumor size and auditory function. This study highlights the inflammatory landscape's impact on VS behaviors, providing a basis for targeted therapeutic strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8335-8353"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622080","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":"Identification of Cellular Senescence-Related Critical Genes and Molecular Classification and Revealing the Drug-Resistant Therapeutic Effect of IGFBP2 in Chronic Myeloid Leukemia.","authors":"Yanmei Xu, Wentao Yang, Fangyi Yao, Zihao Wang, Jing Liu, Bo Huang, Xiaolin Li, Fangmin Zhong, Xiaozhong Wang","doi":"10.2147/JIR.S483705","DOIUrl":"https://doi.org/10.2147/JIR.S483705","url":null,"abstract":"<p><strong>Background: </strong>The occurrence and development of hematologic tumors are closely linked to cellular senescence. However, the molecular characteristics associated with this phenomenon in chronic myeloid leukemia (CML) have not been thoroughly investigated.</p><p><strong>Methods: </strong>The cellular senescence score was calculated using gene set variation analysis. Consensus clustering algorithm was used to identify the molecular subtypes associated with cellular senescence. Clinical samples were collected for sequencing analysis to verify the expression of critical cellular senescence-related genes (CSRG). The effect of targeted inhibition of IGFBP2 on the malignant phenotype of CML-resistant cells was studied by cell experiments.</p><p><strong>Results: </strong>The cellular senescence score in CML samples was significantly lower compared to normal samples. Higher expression of immune checkpoint markers correlated with increased cellular senescence scores. We identified two distinct molecular subtypes (C1 and C2) related to cellular senescence. The C1 subtype exhibited enhanced metabolic function and DNA damage repair capacity, while the C2 subtype showed higher infiltration of immune effector cells and activity in immune-related signaling pathways. We also discovered a group of drugs that displayed significant sensitivity differences between these two molecular subtypes, with the C2 subtype showing greater responsiveness to immunotherapy. Four critical cellular senescence-related genes (CSRGs), namely IGFBP2, IL7R, PLAU, and SUN1 demonstrated high diagnostic value for CML. We validated the expression levels of these four genes using clinical samples and confirmed through cell experiments that targeted inhibition of IGFBP2 effectively suppressed proliferation of resistant CML cells, promoted apoptosis, and enhanced therapeutic sensitivity to imatinib.</p><p><strong>Conclusion: </strong>Our study conducted a comprehensive analysis on CSRG expression characteristics in CML and explored potential correlations between cellular senescence and immune function. The identification of molecular subtypes provides valuable insights into assessing individual patients' biological characteristics for guiding clinical treatment decisions. Additionally, IGFBP2 has emerged as a promising therapeutic target for therapy-resistant cases of CML.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8313-8324"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622100","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}