Journal of Inflammation Research最新文献

{"title":"Cardamonin Attenuates Myocardial Ischemia/Reperfusion-Induced Ferroptosis Through Promoting STAT3 Signaling.","authors":"Tao Yang, Pengcui Wu, Luping Jiang, Ran Chen, Qiao Jin, Guohong Ye","doi":"10.2147/JIR.S486412","DOIUrl":"10.2147/JIR.S486412","url":null,"abstract":"<p><strong>Objective: </strong>Ferroptosis is intricately associated with the pathophysiology processes of myocardial ischemia. Cardamonin (CAR) has been shown to provide significant protection against tissue damage due to multiple ischemia/reperfusion. This study aimed to examine the cardioprotective properties of CAR in myocardial ischemia/reperfusion injury (MIRI) and provide insights into the possible mechanisms involved.</p><p><strong>Methods: </strong>An MIRI mice model was conducted by coronary artery ligation, and the effects of CAR on myocardial tissue damage were evaluated by infarct size assessment, echocardiography, and H&E staining. The extent of ferroptosis was detected by examining the levels of ferroptosis-related proteins and lipid reactive oxygen species (ROS). The function pathway of CAR was analyzed by network pharmacology and verified using Western blotting. In addition, we induced hypoxia/reoxygenation (H/R) in cardiomyocytes to detect SLC7A11 expression, ROS level, mitochondrial iron content, and oxidative stress marker levels. The target protein of CAR was identified by Western blotting and molecular docking. We then evaluated the regulatory role of STAT3 on MIRI-induced ferroptosis by silencing STAT3.</p><p><strong>Results: </strong>In our study, CAR demonstrated a reduction in myocardial histopathological damage and mitigation of ferroptosis in MIRI mice. Through network pharmacology analysis and Western blotting, our findings indicated that CAR modulates the AGE-RAGE signaling pathway, particularly impacting STAT3. Meanwhile, in vitro experiments revealed that advanced-glycation end products (AGEs) exacerbated H/R-induced ferroptosis, whereas CAR alleviated this ferroptosis in the presence of both AGEs and H/R. CAR was observed to enhance STAT3 expression in H/R+AGRs-treated cardiomyocytes. Molecular docking results demonstrated favorable binding interactions between CAR and STAT3. Our study confirmed that CAR mitigated MIRI-induced myocardial injury and ferroptosis through targeting STAT3 in mice.</p><p><strong>Conclusion: </strong>In conclusion, CAR inhibited ferroptosis by activating the STAT3 signaling, thereby mitigating MIRI.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8861-8879"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681757","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":"Serpin B9 is Highly Expressed in Lung Adenocarcinoma and is Associated with Progression-Free Survival.","authors":"Yue Fang, Yi Yue, Sensen Hao, Ying Zhang, Nan Liu, Shengling Wang, Yan Li, Hongzhi Wang","doi":"10.2147/JIR.S472199","DOIUrl":"10.2147/JIR.S472199","url":null,"abstract":"<p><strong>Background: </strong>Serpin B9 is highly expressed in breast cancer, melanoma, and various malignant cells and inhibits NK cell killing through the Serpin B9-GrB axle. However, the current studies have only validated the role of Serpin B9 in vivo and vitro, and lack of systematic studies on the expression of Serpin B9 in patients' tumor tissues and its prognostic implications. In this study, we propose to further validate the role of Serpin B9 by comparing its expression level in tissues of lung adenocarcinoma patients and its correlation with the efficacy of immunotherapy.</p><p><strong>Methods: </strong>This study included 200 patients with LUAD between Feb 2022 and Feb 2023. IHC scoring assessed Serpin B9 expression in the tumor and adjacent tissues, with an H-score of 2 as the cutoff value. Patients were divided into high- and low-expression groups. <i>T</i>-tests were used to compare Serpin B9 expression and treatment efficacy between the tumor and adjacent tissues in both groups. Baseline characteristics were compared using X2 tests. Prognostic risk factors were identified using Cox regression and Kaplan-Meier survival curves.</p><p><strong>Results: </strong>The expression level of Serpin B9 in LUAD tumor tissues are higher than adjacent tissues and positively correlated with the TNM stage and negative correlated with PFS in patients with LUAD. Additionally, immunotherapy efficacy was inversely correlated with Serpin B9 expression.</p><p><strong>Conclusion: </strong>The increased expression of Serpin B9 in LUAD tumor tissues is negatively linked to prognosis and immunotherapy efficacy. This underscores their potential as prognostic and therapeutic targets.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8881-8890"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666987","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":"Hyperresponsiveness of Corticoid-Resistant Th17/Tc-17 Cells to TLR-2 and TLR-4 Ligands is a Feature of Multiple Sclerosis Patients at Higher Risk of Therapy Failure.","authors":"Joana Hygino, Marisa C Sales, Priscila M Sacramento, Taissa M Kasahara, Júlio César Costa da Silva, Rafaela Bilhão, Regis M Andrade, Cláudia Cristina Ferreira Vasconcelos, Cleonice A M Bento","doi":"10.2147/JIR.S476110","DOIUrl":"10.2147/JIR.S476110","url":null,"abstract":"<p><strong>Purpose: </strong>The presence of T cells expressing TLR-2 and TLR-4 has been associated with relapsing-remitting multiple sclerosis (RRMS) pathogenesis. Here, we evaluated whether the effectiveness of DMT in controlling clinical activity of the disease would be associated with modulation of proportion of TLRs⁺ T cells.</p><p><strong>Patients and methods: </strong>Whole peripheral blood mononuclear cells, purified CD4⁺ and CD8⁺ T cells from RRMS patients were cultured with different stimuli. The frequency of IL-17-secreting CD4⁺ and CD8⁺ T cells positive for TLR-2 and TLR-4 was determined by flow cytometry. The cytokine profile of these T cells following TLR-2 and TLR-4 stimulation was determined by Multiplex. Some of these T cell cultures were treated with hydrocortisone. The levels of LPS-binding protein (LBP) were dosed by ELISA. Clinical (occurrence of relapses) and radiological (number of active brain lesions) activity were evaluated during the 1-year follow-up.</p><p><strong>Results: </strong>Despite DMT, high intensity of TLR-2 and TLR-4 expression on (CD4⁺ and CD8⁺) T-cells, as well as the frequency of IL-17-secreting (CD4⁺ and CD8⁺) T-cells, are predictive of future RRMS relapses. Moreover, higher cytokine production related to Th17/Tc-17 phenotypes in response to TLR-2 and TLR-4 agonists was observed in DMT-treated patients and displayed an elevated number of brain lesions. The hyperresponsiveness of MS-derived T-cells to TLR-2 and TLR-4 ligands, with high levels of IL-1β, IL-6, IL-17, IFN-γ and GM-CSF in response to both TLR agonists, positively correlated with plasma LBP levels. Interestingly, corticoid was less efficient in reducing Th17 and Tc-17 cytokine production induced by TLR-2 and TLR-4 ligands in DMT-treated patients who relapsed during follow-up.</p><p><strong>Conclusion: </strong>Collectively, the data suggested that persistence of circulating Th17 and Tc17 cells expressing elevated levels of functional TLR-2 and TLR-4 could indicate high disease activity and lower therapeutic efficacy in RRMS patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8775-8797"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675904","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":"The First Case of Felty's Syndrome Complicated by COVID-19 Infection.","authors":"Yueming Li, Fanyou Zhu, Rui Wen, Tingting Hou, Rou Xie, Jiao Qin","doi":"10.2147/JIR.S479377","DOIUrl":"10.2147/JIR.S479377","url":null,"abstract":"<p><p>Felty's syndrome (FS) is an uncommon disorder with a poor prognosis, and most patients die from infections caused by neutropenia. Currently, there is no standardized treatment strategy, and treatment options are based on case reports and clinical experience. To date, no cases of FS complicated by coronavirus disease-2019 (COVID-19) have been reported. This article reports a successful case of FS complicated by COVID-19. We emphasized treating rheumatic diseases with immunosuppressive therapy at appropriate doses based on strong and effective anti-infection when co-infected.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8853-8860"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667524","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 and Validating the Mechanism of Ulinastatin in the Treatment of Sepsis-Associated Encephalopathy Based on Transcriptome Sequencing.","authors":"Wen Hu, Xiaoyuan Zhang, Zhen Wu, Yushan Luo, Bailong Hu, Xiaohua Zou","doi":"10.2147/JIR.S488400","DOIUrl":"10.2147/JIR.S488400","url":null,"abstract":"<p><strong>Purpose: </strong>Sepsis can induce sepsis-associated encephalopathy (SAE), with Ulinastatin (UTI) serving a critical anti-inflammatory role. This study aimed to identify the hub genes in an SAE mouse model following UTI intervention and investigate the underlying molecular mechanisms.</p><p><strong>Materials and methods: </strong>Through differential expression analysis to obtain differentially expressed genes (DEGs), ie, UTI vs CLP (DEGs1) and Con vs CLP (DEGs2). After taking the intersection of the genes with opposite differential trends in these two parts and immune-related genes (IRGs), DE-IRGs were obtained. Hub genes in the protein-protein interaction (PPI) network were then determined using six algorithms from the Cytohubba plugin in Cytoscape. Gene set enrichment analysis (GSEA) was employed to explore the functional relevance of these hub genes. Additionally, the immune microenvironment across the three groups was compared, and hub gene-related drugs were predicted using an online database. Finally, qRT-PCR was used to validate the expression of the hub genes in hippocampal tissue from CLP mice.</p><p><strong>Results: </strong>RNA sequencing obtained 864 differentially expressed genes (DEGs) (CLP vs Con) and 279 DEGs (UTI vs CLP). Taking the intersection of DEGs with opposite expression trends yielded 165 DEGs. Six key genes (ICAM - 1, IRF7, IL - 1β, CCL2, IL - 6 and SOCS3) were screened by six algorithms. Immune infiltration analysis found that Treg cells were reversed after treatment with UTI in the diseased state. A total of 106 hub - gene - related drugs were predicted, among which BINDARIT - CCL2 and LIFITEGRAST - ICAM1 showed particularly high affinities. The qRT - PCR verification results were consistent with the sequencing results.</p><p><strong>Conclusion: </strong>In conclusion, <i>ICAM-1, IRF7, IL-1β, CCL2, IL-6</i>, and <i>SOCS3</i> were identified as potential therapeutic targets in SAE mice treated with UTI. This study offers theoretical support for UTI as a treatment option for SAE.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8753-8773"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675903","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":"Associations Between Preoperative Inflammatory Indices and Residual or Recurrent Cervical Intraepithelial Neoplasia Post Loop Electrosurgical Excision Procedure.","authors":"Furui Zhai, Shanshan Mu, Yinghui Song, Min Zhang, Cui Zhang, Ze Lv","doi":"10.2147/JIR.S485698","DOIUrl":"10.2147/JIR.S485698","url":null,"abstract":"<p><strong>Background: </strong>High-grade cervical intraepithelial neoplasia (CIN2/3) is a precursor to invasive cervical cancer, necessitating effective management. While the Loop Electrosurgical Excision Procedure (LEEP) is a successful treatment, recurrence remains a significant concern. This study evaluates the predictive value of preoperative immune-inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), in assessing the risk of residual or recurrent CIN post-LEEP.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 423 women who underwent LEEP for CIN2/3 at Cangzhou Central Hospital between 2016 and 2020. Cox proportional hazards regression models with restricted cubic splines were used to evaluate linear and non-linear associations between immune-inflammatory indices and recurrence risk. Multivariate models were adjusted for confounding factors, and subgroup analyses were conducted to test the robustness of the associations. Threshold non-linear fitting and saturation effect analyses were also performed to identify inflection points influencing residual or recurrent disease risk.</p><p><strong>Results: </strong>Significant differences in age, menopausal status, TCT results, HPV status, degrees of CIN and margin status were observed between recurrence and non-recurrence groups. NLR demonstrated a U-shaped relationship with recurrence risk, with a threshold effect. NLR values below 3.15 were associated with a reduced recurrence risk, while higher values increased the risk. PLR and SII showed a modest protective effect below their respective thresholds.</p><p><strong>Conclusion: </strong>Systemic inflammation plays a key role in CIN recurrence following LEEP. NLR serves as a valuable prognostic marker, highlighting the potential for personalised follow-up strategies. Further research is needed to confirm these findings and elucidate the underlying mechanisms.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8741-8751"},"PeriodicalIF":4.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666460","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":"Development of a Nomogram Based on Transcriptional Signatures, IFN-γ Response and Neutrophils for Diagnosis of Tuberculosis.","authors":"Yan-Hua Liu, Jin-Wen Su, Jing Jiang, Bing-Fen Yang, Zhi-Hong Cao, Fei Zhai, Wen-Na Sun, Ling-Xia Zhang, Xiao-Xing Cheng","doi":"10.2147/JIR.S480173","DOIUrl":"10.2147/JIR.S480173","url":null,"abstract":"<p><strong>Purpose: </strong>Tuberculosis (TB) is a major global health threat and its diagnosis remains challenging. This study aimed to develop a nomogram that incorporated peripheral blood transcriptional signatures and other blood tests for the diagnosis of tuberculosis.</p><p><strong>Patients and methods: </strong>Patients with TB, patients with other definite pulmonary diseases (OPD), individuals with latent tuberculosis infection (LTBI), and healthy controls (HC) were retrospectively enrolled between May 2017 and April 2018. The results of the interferon-γ release assay (IGRA) and blood counts were obtained from medical records, and the transcripts of 10 genes were detected using reverse transcription polymerase chain reaction (RT-PCR). Variable selection was performed using least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression was performed for the optimal prediction model with backward direction. The model was displayed as a nomogram, and its performance was evaluated for discrimination ability, calibration ability, and clinical usefulness. Internal validation of the prediction model was conducted using bootstrap resampling.</p><p><strong>Results: </strong>A total of 185 participants were enrolled, including 84 patients with TB and 101 controls. A prediction nomogram composed of IGRA, percentage of neutrophils, and expression levels of CD64, granzyme A (GZMA), and PR/SET domain 1 (PRDM1) was established. The nomogram demonstrated good discrimination, with an unadjusted area under the curve (AUC) of 0.914 (95% CI: 0.875-0.954) and a bootstrap-corrected AUC of 0.914 (95% CI: 0.874-0.947). With a cutoff value of 0.519, the sensitivity and specificity for discriminating PTB from controls were 0.81 and 0.871, respectively. The nomogram also showed good calibration with the Hosmer-Lemeshow test (P=0.58) and good clinical practicality displayed by the decision curve analysis.</p><p><strong>Conclusion: </strong>A nomogram composed of IGRA, percentage of neutrophils, and expression of CD64, GZMA, and PRDM1 was established. The nomogram demonstrated a sensitivity and specificity of 81% and 87%, respectively, for differentiating TB from controls.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8799-8811"},"PeriodicalIF":4.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666758","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":"Unveiling the Molecular Links Between Atrial Fibrillation and Atherosclerosis: Insights into Shared Pathogenesis and Ferroptosis Diagnostic Biomarkers.","authors":"Bowen Xu, Hongye Li, Hongping Chen, Da Teng, Lei Gong, Lin Zhong, Jun Yang","doi":"10.2147/JIR.S488288","DOIUrl":"10.2147/JIR.S488288","url":null,"abstract":"<p><strong>Objective: </strong>Atherosclerosis(AS) is a vascular disease characterized by the development of plaque in the arteries, and atrial fibrillation (AF) is a common heart arrhythmia. These two conditions share several risk factors in common, such as aging, diabetes, obesity, and hypertension. Ferroptosis is a new mode of non-apoptotic cell death that plays a key role in cardiomyocyte death and has been associated with a variety of cardiac diseases. This study aimed to investigate the ferroptosis biomarkers and underlying biological mechanisms associated with AF and AS.</p><p><strong>Materials and methods: </strong>The gene expression dataset was obtained from GEO database, differentially expressed genes (DEGs) and ferroptosis expressed genes (FDGs) were obtained by data processing and screening, and then functional enrichment, network construction, transcription factor prediction, identification of biomarkers by LASSO and SVM - RFE algorithms, and also immune infiltration analyses and cellular experiments were performed.</p><p><strong>Results: </strong>In AF and AS, 1627 and 571 DEGs were identified respectively, and 128 were intersected, and 47 common FDGs were also identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs revealed that they were associated with biological processes and pathways such as leukocyte immunity, and FDGs were also involved in specific functions and pathways. Fifteen key genes were identified, CSF1R and ITGAM expression differences were verified, and seven transcription factors were predicted to be differentially expressed. Characterized genes were screened to construct models with good diagnostic efficacy, and immune infiltration showed that NUPR1 was associated with altered immune environments, and WB indicated that NUPR1 was highly expressed in the disease model.</p><p><strong>Conclusion: </strong>Our study demonstrates that the ferroptosis gene NUPR1 plays a role in the pathogenesis of atrial fibrillation and atherosclerosis, and also provides valuable insights into their molecular mechanisms, which may contribute to the development of new targets and strategies for the treatment of these diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8813-8830"},"PeriodicalIF":4.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667464","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":"Gain-of-Function Variant in Spleen Tyrosine Kinase Regulates Macrophage Migration and Functions to Promote Intestinal Inflammation.","authors":"Ye Yang, Lin Wang, Zhiyang Zeng, Chunmeng He, Yanqiu Wang, Ying Huang","doi":"10.2147/JIR.S488901","DOIUrl":"10.2147/JIR.S488901","url":null,"abstract":"<p><strong>Purpose: </strong>Spleen tyrosine kinase (Syk) is a widely-expressed cytoplasmic non-receptor tyrosine kinase involved in regulating various signaling pathways and plays an important role in chronic inflammation and autoimmune diseases. Gain-of-function <i>SYK</i> variants have been implicated in pediatric inflammatory bowel diseases. This study aimed to investigate the effects of gain-of-function <i>SYK</i> variants on the susceptibility to experimental colitis and macrophage function.</p><p><strong>Methods: </strong>Colitis was induced using dextran sodium sulfate and dinitrobenzene sulfonic acid in mice harboring a gain-of-function variant in <i>SYK</i> (Syk^S544Y). Intestinal inflammation was assessed via disease activity index, histological analysis, and Western blotting. The frequencies of macrophages, phagocytosis, and reactive oxygen species (ROS) production in bone marrow-derived macrophages (BMDM) were measured via flow cytometry. Chemokines and BMDM chemotaxis were analyzed using real-time quantitative reverse transcription polymerase chain reaction and Transwell assays. The expression of nucleotide-binding domain leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome-related proteins were detected using immunohistochemistry, enzyme-linked immunoassay and Western blotting.</p><p><strong>Results: </strong>Syk^S544Y mice exhibited increased susceptibility to experimental colitis, and macrophage infiltration in colon tissues significantly increased. We observed increased expression of macrophage chemokines in colon tissues and enhanced chemotaxis in Syk^S544Y BMDM. Additionally, we detected increased levels of fluorescent microspheres and 2.7-dichloride-hydro fluorescein diacetate-labeled ROS in Syk^S544Y BMDM. Moreover, enhanced levels of NLRP3 inflammasome-related proteins were observed in the colon tissues and BMDM from Syk^S544Y mice.</p><p><strong>Conclusion: </strong>Gain-of-function variant in <i>SYK</i> may contribute to the pathogenesis of pediatric inflammatory bowel diseases by promoting macrophage migration, phagocytosis, ROS production and activation of NLRP3 inflammasomes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8713-8726"},"PeriodicalIF":4.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666986","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":"Predictive Value of the Systemic Immune-Inflammation Index in the 28-Day Mortality for Patients with Sepsis-Associated Acute Kidney Injury and Construction of a Prediction Model.","authors":"Lijuan Zhang, Liyan Liu, Guosheng Yan, Xu Ma, Guizhen Zhu, Xinxin Dong, Yang Lu, Hongtao Zhang","doi":"10.2147/JIR.S488900","DOIUrl":"10.2147/JIR.S488900","url":null,"abstract":"<p><strong>Purpose: </strong>The predictive value of the Systemic Immune-Inflammation Index (SII) on mortality in patients with sepsis-associated acute kidney injury (S-AKI) remains unclear. This study aims to investigate the predictive value of SII levels at the Intensive Care Unit (ICU) on the 28-day mortality of S-AKI patients.</p><p><strong>Patients and methods: </strong>S-AKI patients admitted to the ICU of Henan Provincial People's Hospital from January 1, 2023, to December 31, 2023. Patients who were diagnosed with S-AKI were divided into survival and death groups based on their 28-day outcome after ICU admission. Using receiver operating characteristic (ROC) curves to determine the best cut-off values and prognostic abilities of various parameters. Kaplan-Meier survival curves describe the 28-day survival of patients after ICU admission. Cox regression analysis identified the main risk factors associated with mortality in S-AKI patients, constructing a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability of this model.</p><p><strong>Results: </strong>A total of 216 patients with S-AKI were included. ROC analysis showed that SII had the highest predictive value for mortality risk in S-AKI patients after ICU admission. Compared with the low-SII group, the high-SII group had higher 28-day (86.7% vs 32.4%, respectively, P <0.001) mortality rate. Based on Cox regression analysis, a nomogram predictive model was constructed, including age, respiratory failure, SII levels, number of organ dysfunctions at ICU admission, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHEII). The C-index for predicting the 28-day survival rate was 0.682. Decision curve analysis indicated a high level of clinical predictive efficacy.</p><p><strong>Conclusion: </strong>SII serves as a potential biomarker for predicting the prognosis of S-AKI patients. The constructed nomogram prognostic model can aid in assessing the prognosis of S-AKI patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8727-8739"},"PeriodicalIF":4.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648219","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}