Journal of Inflammation Research最新文献

{"title":"Dynamic Trends of Albumin-to-C-Reactive Protein Ratio: A Prognostic Indicator in Elderly Patients with Community-Acquired Pneumonia.","authors":"Lei Miao, Chen Gong, Jingxian Liao, Chunhui Xie, Xiaozhu Shen, Yajuan Cheng","doi":"10.2147/JIR.S512632","DOIUrl":"10.2147/JIR.S512632","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of dynamic changes in the albumin-to-C-reactive protein ratio (ACR) in elderly patients with community-acquired pneumonia (CAP) has not been fully elucidated. This study aims to evaluate the utility of ACR as a dynamic biomarker for predicting 28-day mortality and enhancing risk stratification in this high-risk population.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on 437 elderly CAP patients (≥65 years). Serum albumin and C-reactive protein (CRP) levels were measured at admission (T0), 24 hours (T1), and 3 days (T2) post-admission. ACR was calculated for each time point, and its prognostic value was assessed using advanced statistical methods.</p><p><strong>Results: </strong>The 28-day mortality rate was 16.7%. ACR levels were consistently lower in non-survivors across all time points (P < 0.001). RCS analysis revealed a nonlinear relationship between ACR and mortality risk. Time-varying ROC analysis demonstrated that ACR consistently outperformed CRP in predicting mortality, with superior area under the curve (AUC) values at all time points. Random-effects modeling indicated minimal inter-individual variability in ACR (random effects variance: 0.030; standard deviation: 0.175). Time-varying Cox regression confirmed a strong negative association between dynamic ACR changes and mortality risk, with a C-statistic of 0.833 (P < 0.001).</p><p><strong>Conclusion: </strong>Dynamic monitoring of ACR is a robust and clinically applicable tool for predicting short-term mortality in elderly CAP patients. By integrating markers of inflammation and nutritional status, ACR facilitates early identification of high-risk patients and supports personalized treatment strategies. These findings highlight the potential of ACR as a novel biomarker for improving clinical outcomes in this vulnerable population.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4195-4211"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692561","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 Disulfidptosis-Related Genes and Molecular Subgroups in Rheumatoid Arthritis for Diagnostic Model and Patient Stratification.","authors":"Xinyi Liu, Siyao Wang, Xinru Du, Yulu Wang, Lingfei Mo, Hanchao Li, Zechao Qu, Xiaohao Wang, Jian Sun, Yuanyuan Li, Jing Wang","doi":"10.2147/JIR.S505746","DOIUrl":"10.2147/JIR.S505746","url":null,"abstract":"<p><strong>Introduction: </strong>Cell death contributes to the pathogenesis of rheumatoid arthritis (RA) through various pathways. Disulfidptosis is a recently discovered novel form of cell death characterized by the abnormal accumulation of intracellular disulfide bonds. It remains unclear for the association between RA and disulfidptosis.</p><p><strong>Methods: </strong>A comprehensive analysis of three GEO datasets was presented in this study. First, the analysis involved the use of weighted gene co-expression network analysis (WGCNA) and differential analysis and were employed to identify the key module genes related to RA and disulfidptosis-related genes. The machine learning algorithms were used to identify the hub genes. Second, a diagnostic model was constructed for RA based on the hub genes. The nomogram and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic value of the model. Third, two RA subtypes were identified based on hub genes by using consensus clustering analysis. Then, the disease activity scores, clinical markers, and immune cells were compared between the two RA subgroups. Finally, the differential expression of hub genes was validated between healthy controls and RA patients by qPCR.</p><p><strong>Results: </strong>Four hub genes (KLHL2, POLK, CLEC4D, NXT2) were identified. The expression of the four hub genes was verified to be significantly higher in RA patients compared with healthy controls. The superior diagnostic value of the model was validated, which demonstrated that the model outperforms each hub gene individually. Two subtypes of RA were determined. Patients in cluster A exhibited relatively lower levels of DAS28-CRP, DAS28-ESR, CDAI, SDAI, RF, CRP, and MMP3. In contrast, patients in cluster B had significantly higher levels of the above markers.</p><p><strong>Conclusion: </strong>Four hub genes were identified to provide unique insights into the role of disulfidptosis in RA. Additionally, a promising diagnosis model and patient stratification were established based on the hub genes to assess the risk of RA onset and RA disease activity.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4157-4175"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692591","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":"Differential Diagnosis Value of Neutrophil Gelatinase Associated Lipocalin as a Noninvasive Biomarker in Perianal Fistulizing Crohn's Disease.","authors":"Kai Ma, Yikun Li, Jingwen Wu, Yi Fu, Lu Yin, Simin Xu, Feiyang Weng, Yibo Yao, Chen Wang","doi":"10.2147/JIR.S504213","DOIUrl":"10.2147/JIR.S504213","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing perianal fistulizing Crohn's disease (pfCD) typically depends on costly and time-intensive endoscopic and radiographic procedures. Compelling evidence indicates that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the pathophysiology of Crohn's disease (CD) and may serve as a noninvasive biomarker for its diagnosis. This study aimed to evaluate NGAL's potential as a noninvasive diagnostic biomarker between pfCD and cryptoglandular (CG) perianal fistula, and its correlation with disease severity in pfCD.</p><p><strong>Methods: </strong>Serum, fecal, and fistula tissue samples were collected from 96 patients with pfCD and 97 patients with CG perianal fistula as controls. Serum NGAL levels were quantified through ELISA and fistula tissue NGAL levels were quantified through immunohistochemical staining, while pfCD disease severity was evaluated using the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). Additional laboratory parameters, including NGAL, fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were analyzed, and their correlations were assessed. Receiver operating characteristic (ROC) analysis was conducted to evaluate NGAL's diagnostic potential for pfCD.</p><p><strong>Results: </strong>Levels of serum NGAL, FC, CRP, and ESR in patients with pfCD were significantly elevated compared to the control group (<i>p</i> < 0.001); Spearman correlation analysis indicated a positive correlation between serum NGAL and FC, CRP, ESR, CDAI, and PDAI scores. The area under the ROC curve (AUC) for serum NGAL in diagnosing pfCD was 0.927 (95% <i>CI</i>: 0.890-0.964). The AUC for FC in diagnosing pfCD were 0.887 (95% <i>CI</i>: 0.839-0.935). Additionally, serum and fistula tissue NGAL levels were positively correlated with disease complexity in pfCD according to the Montreal classification.</p><p><strong>Conclusion: </strong>These findings suggest that serum NGAL is associated with pfCD severity and may offer a promising noninvasive biomarker for diagnosing and assessing pfCD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4075-4086"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692495","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":"LT-α Facilitates the Aerobic Glycolysis and M1 Polarization of Macrophages by Activating the NF-κB Signaling Pathway in Intervertebral Disc Degeneration.","authors":"Chensheng Qiu, Zhu Guo, Junhua Yuan, Hongfei Xiang, Bohua Chen, Yuanxue Yi, Yongsheng Zhao","doi":"10.2147/JIR.S506162","DOIUrl":"10.2147/JIR.S506162","url":null,"abstract":"<p><strong>Purpose: </strong>Injury and inflammatory activate and polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried to explore the mechanisms that regulate macrophage polarization, providing new insights and targets for IVDD treatment. The aim of our study was to evaluate the influence of LT-α on aerobic glycolysis (AG) and polarization in macrophages.</p><p><strong>Methods: </strong>M0 macrophages were achieved by stimulating THP-1 cells with PMA. M1 macrophages were obtained by IFN-γ and LPS stimulation in M0 macrophages. Energy metabolomics, AG and apoptosis related protein expression, migration and invasion measurement, proliferation was analyzed. Polarization of macrophages, AG associated genes expression, macrophage recruitment was evaluated. NF-κB signaling was ascertained by laser confocal and Western blotting.</p><p><strong>Results: </strong>The propanoate metabolism pathway was enriched in LT-α overexpressing M0 macrophages, and various energy metabolites were detected. Glucose absorption, lactic acid production, and levels of AG proteins were strikingly increased in LT-α overexpression macrophages and remarkably repressed in LT-α knockdown macrophages, accompanied by activated and inactivated NF-κB signaling, respectively. Suppressed migration and invasion ability, restrained proliferation, activated AG, and enhanced apoptosis were observed in nucleus pulposus (NP) cells treated by LT-α overexpressed macrophages, accompanied by reduced macrophage recruitment, with opposite results when treated by LT-α knockdown macrophages. The enhanced M1 polarization and activated AG in LT-α overexpression macrophages were abolished by co-culturing with NF-κB inhibitor.</p><p><strong>Conclusion: </strong>LT-α facilitates the AG and M1 polarization of macrophages via activating the NF-κB signaling pathway.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4103-4120"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692540","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":"Osteoimmunology in Osteoarthritis: Unraveling the Interplay of Immunity, Inflammation, and Joint Degeneration.","authors":"Kangyi Hu, Min Song, Ting Song, Xiao Jia, Yongjia Song","doi":"10.2147/JIR.S514002","DOIUrl":"10.2147/JIR.S514002","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a degenerative joint disease influenced by multiple factors, with its etiology arising from intricate interactions among mechanical stress, inflammatory processes, and disruptions in bone metabolism. Recent research in bone immunology indicates that immune-mediated mechanisms significantly contribute to the progression of OA, highlighting the interactions among immune cells, cytokine networks, and bone components. Immune cells interact with osteoclasts, osteoblasts, and chondrocytes in a variety of ways. These interactions foster a pro-inflammatory microenvironment, contributing to cartilage breakdown, synovial inflammation, and the sclerosis of subchondral bone. In this article, we present a comprehensive review of bone immunology in OA, focusing on the critical role of immune cells and their cytokine-mediated feedback loops in the pathophysiology of OA. In addition, we are exploring novel therapeutic strategies targeting bone immune pathways, including macrophage polarization, T-cell differentiation, and stem cell therapy to restore the metabolic balance between immunity and bone. By integrating cutting-edge research in bone immunology, this review integrates the latest advancements in bone immunology to construct a comprehensive framework for unraveling the pathogenesis of OA, laying a theoretical foundation for the development of innovative precision therapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4121-4142"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692570","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":"Combining Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation to Uncover the Efficacy and Mechanisms of Si-Miao-Yong-An Decoction in Diabetic Wound Healing.","authors":"Shujuan Zhang, Yiming Shao, Ranran Jin, Baodong Ma","doi":"10.2147/JIR.S506739","DOIUrl":"10.2147/JIR.S506739","url":null,"abstract":"<p><strong>Purpose: </strong>Si-Miao-Yong-An (SMYA) Decoction, a traditional Chinese herbal mixture, shows promise for managing diabetic complications. Up to this point, no reports have explored the effects of SMYA on diabetic wounds or the underlying mechanisms. This study aimed to investigate the therapeutic potential of SMYA in promoting diabetic wound healing and to elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The wound healing effects of SMYA were evaluated in db/db diabetic mice by measuring wound closure rates and histological characteristics, including epidermal thickness and collagen deposition. Network pharmacology was utilized to identify active ingredients and corresponding therapeutic targets of SMYA, followed by validation through molecular docking and molecular dynamics simulations. KEGG and GO enrichment analyses were conducted to elucidate the relevant biological processes and pathways. In vitro studies involving high-glucose-treated HUVECs assessed the effects of SMYA-containing serum on cellular migration and angiogenesis. Finally, the expression of inflammatory factors and RAGE in the wound tissue was detected by qRT-PCR.</p><p><strong>Results: </strong>SMYA significantly accelerated wound closure in db/db mice, as evidenced by improved epidermal thickness, tissue morphology, and collagen deposition. Network pharmacology identified 140 overlapping genes involved in angiogenesis and inflammation, with the AGE-RAGE signaling pathway playing a central role. Molecular docking and dynamics simulations revealed strong binding stability of quercetin and kaempferol to inflammation-related hub targets, including IL-6, TNF, and IL-1β. In vitro, SMYA-containing serum alleviated high-glucose-induced impairments in HUVEC migration and angiogenesis. Furthermore, qRT-PCR analysis showed that SMYA significantly downregulated Tnf, Il1b, Il6, and Rage expression in wound tissues, supporting its anti-inflammatory effect.</p><p><strong>Conclusion: </strong>SMYA promotes diabetic wound healing by modulating the inflammatory microenvironment and inhibiting the AGE-RAGE signaling pathway. These findings provide robust evidence for SMYA's therapeutic potential and lay a foundation for its future clinical application in treating diabetic wounds.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4087-4101"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700510","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":"DNA-PKcs Dysfunction Enhances the Antitumor Activity of Radioimmunotherapy by Activating the cGAS-STING Pathway in HNSCC.","authors":"Lizhu Chen, Jing Lin, Yaoming Wen, Zeng-Qing Guo, Bin Lan, Jiani Xiong, Chuan-Ben Chen, Yu Chen","doi":"10.2147/JIR.S497295","DOIUrl":"10.2147/JIR.S497295","url":null,"abstract":"<p><strong>Introduction: </strong>Combining radiotherapy (RT) with immunotherapy for head and neck squamous cell carcinoma (HNSCC) has limited effectiveness due to the DNA damage repair (DDR) pathway activated by ionizing radiation. DNA-PK, encoded by the <i>PRKDC</i> gene, plays a key role in this repair. The potential improvement of radioimmunotherapy by inhibiting the DDR pathway is still unclear.</p><p><strong>Methods: </strong>The effectiveness of different treatments on tumor growth and survival was tested using the C3H/HeN mouse tumor model. Flow cytometry analyzed treatment-induced immunophenotypic changes. In vitro, Western blot and PCR confirmed the impact of combining immunotherapy with RT on the cGAS-STING pathway after DNA-PKcs dysfunction.</p><p><strong>Results: </strong>The combination of a DNA-PK inhibitor (NU7441), radiation therapy, and a PD-1 checkpoint inhibitor showed improved antitumor effects and extended survival in mice. Adding NU7441 into the RT and immunotherapy regimen increased CD8+ T cell infiltration. <i>PRKDC</i> alterations or DNA-PKcs dysfunction increased IR-induced DNA breaks, activating the cGAS-STING pathway and boosting the anti-tumor immune response.</p><p><strong>Conclusion: </strong>These findings suggest that targeting the DDR pathway may represent a promising therapeutic strategy and biomarker to improve the efficacy of radioimmunotherapy in HNSCC.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4177-4193"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700515","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":"Cordyceps Sinensis Reduces Inflammation and Protects BEAS-2B Cells From LPS-Induced THP-1 Cell Injury.","authors":"Xiaqing Wu, Xin Li, Ying Chai, Yushan Tian, Hongjuan Wang, Xiao Li, Jingzheng Zhang, Chunmei Guang, Enliang Hong, Haoping Cheng, Qingyuan Hu, Huan Chen, Hongwei Hou","doi":"10.2147/JIR.S508098","DOIUrl":"10.2147/JIR.S508098","url":null,"abstract":"<p><strong>Introduction: </strong>Cordyceps sinensis, an entomogenous fungus with unique biological properties, has demonstrated significant anti-inflammatory potential. However, its effects on inflammation regulation need to be further investigated in detail.</p><p><strong>Methods: </strong>In this study, we aimed to analyze the Cordyceps sinensis extract (CSE) obtained via ethanol extraction and to assess its effects on inflammation regulation. The secretion of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β) and the level of MMP9, Nrf2/HO-1 and ROS were evaluated. A transwell system with THP-1 and BEAS-2B cells was used to explore the inflammatory damage. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted on the differentially expressed genes.</p><p><strong>Results: </strong>CSE exhibited no cytotoxicity to THP-1 cells at concentrations ≤ 1.6 mg/mL. Treatment of LPS-induced THP-1 cells with CSE significantly inhibited the secretion of pro-inflammatory cytokines. CSE reduced inflammation-related protein MMP9, while upregulating the anti-inflammatory Nrf2/HO-1 signaling pathway. Fluorescence assays using DCF and JC-1 further confirmed that CSE help mitigate oxidative stress-induced inflammation. CSE treatment protected BEAS-2B cells from inflammatory damage. Moreover, the immune system process was a shared GO term between LPS-only treatment and combined LPS and CSE treatment. KEGG enrichment analysis showed that CSE is capable of regulating genes associated with inflammatory and anti-inflammatory responses.</p><p><strong>Conclusion: </strong>These findings highlight the potential of CSE as an immune-regulating agent in functional foods and health products.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4143-4156"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692532","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":"Causal Correlations Between Plasma Metabolites, Inflammatory Proteins, and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization and Bioinformatics-Based Investigation.","authors":"Shurui Cao, Yongqi Gu, Guye Lu, Lizhen Zhu, Shumin Feng, Tao Bian","doi":"10.2147/JIR.S513526","DOIUrl":"10.2147/JIR.S513526","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of studies have demonstrated a strong correlation between metabolism, inflammation, and chronic obstructive pulmonary disease (COPD). However, it remains unclear if there is a causal relationship between these factors. This study employed the Mendelian randomization (MR) approach to investigate the associations between these factors and explore the mediating roles of key inflammatory proteins.</p><p><strong>Methods: </strong>MR was used to assess the causal associations between plasma metabolites, inflammatory proteins, and COPD. Sensitivity analyses were performed to verify the robustness of the findings. Mediation analysis was conducted to explore the roles of inflammatory proteins in the metabolism-COPD pathway. We constructed protein-protein interaction (PPI) network and explored the potential mechanism through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Single-cell sequencing and transcriptome datasets were used for auxiliary validation. Finally, experimental validation was performed using human lung tissue.</p><p><strong>Results: </strong>This study identified 63 metabolites, 10 metabolite ratios, and 48 inflammatory proteins that were associated with COPD, all of which exhibited potential causal relationships. Furthermore, three proteins were identified as mediators in the metabolite-to-COPD pathway. PPI network, GO and KEGG enrichment analysis revealed the biological pathways in which they were involved. Validation of the expression of these three intermediary proteins in lung tissue demonstrated that NRXN3 was expressed in pulmonary endothelial cells and exerted a protective effect against COPD development.</p><p><strong>Conclusion: </strong>The MR analysis revealed causal associations among metabolism, inflammation, and COPD. These findings offer novel insights into metabolism-inflammation-COPD mechanisms, suggesting that interventions targeting metabolic processes may represent a promising strategy for preventing the onset or progression of COPD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4057-4073"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692531","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":"Delirium is a Potential Predictor of Unfavorable Long-term Functional Outcomes in Patients with Acute Ischemic Stroke: A Prospective Observational Study.","authors":"Chenhui Lin, Heyu Zhang, Fangyi Xiao, Yujie Tu, Yaoyao Lin, Luqian Zhan, Yisi Lin, Yanwei Li, Chenglong Xie, Yanyan Chen","doi":"10.2147/JIR.S505038","DOIUrl":"10.2147/JIR.S505038","url":null,"abstract":"<p><strong>Purpose: </strong>Delirium is an acute fluctuating impairment of attention and awareness, common in acute ischemic stroke (AIS). This study aimed to evaluate the prognostic significance of delirium for neurological function at 3 months post-stroke, and develop a predictive model integrating delirium and biomarkers to enhance prognostic accuracy.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of patients admitted to the stroke unit (n=722). All patients were screened for daily delirium during clinical care. Plasma biomarkers were measured within 24 hours after admission. The main outcomes were evaluated with the 3-months modified Rankin Scale (mRS).</p><p><strong>Results: </strong>Delirium developed in 10.2% of patients during the acute phase of stroke. Patients with post-stroke delirium (PSD) was significantly older (median age 74 vs 68 years, <i>P</i><0.001), more likely to have pre-stroke cognitive impairment (14.9% vs 4.8%, <i>P</i>=0.001), a higher prevalence of cardiovascular history (35.1% vs 16.2%, <i>P</i><0.001). PSD was also associated with higher scores of NIHSS (14.3 vs 9.1, <i>P</i><0.001) and greater scores of mRS (3.0 vs 1.5, <i>P</i><0.001) at admission. PSD patients showed worse outcomes, with elevated NIHSS and mRS scores at discharge and 3-month follow-up, as well as higher mortality rates (5.4% vs 1.4%, <i>P</i>=0.025). Biomarker analysis revealed increased plasma levels of inflammatory (white blood cells, neutrophils, C-reactive protein) and coagulation biomarkers (fibrinogen, D-dimer) in PSD patients, particularly those with poorer outcomes (<i>P</i><0.01). Our model, which incorporated delirium and biomarkers of inflammation and coagulation dysfunction, demonstrated strong predictive accuracy for adverse outcomes at 3 months with an AUC of 0.779 (95% CI=0.736-0.822), with clinical utility confirmed by decision curve analysis.</p><p><strong>Conclusion: </strong>PSD is a strong independent predictor of poor 3-month outcomes in AIS, including higher mortality and disability. Our findings highlight the critical role of inflammation and coagulation dysfunction in the pathogenesis of PSD. Furthermore, we present the clinical utility of a predictive model integrating delirium and relevant biomarkers to assess the risk of adverse outcomes at 3 months, suggesting potential targets for intervention.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4019-4035"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692479","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}