Journal of Inflammation Research最新文献

{"title":"TMAO Induces Vascular Endothelial Cells Pyroptosis Through TET2-CYTB-ROS Pathway.","authors":"Linzhen Xia, Zuo Wang, Xiangyu Chen","doi":"10.2147/JIR.S527437","DOIUrl":"10.2147/JIR.S527437","url":null,"abstract":"<p><strong>Purpose: </strong>The study was aimed at identifying that cytochrome b (CYTB) expression regulation by trimethylamine N-oxide (TMAO) can induce mitochondria reactive oxygen species (ROS) and promote vascular endothelial cells (VECs) pyroptosis.</p><p><strong>Methods: </strong>VECs were transfected with TET methylcytosine dioxygenase 2 (TET2)/CYTB overexpression lentivirus, CYTB siRNA, TET2 shRNA, or NC. ROS levels were measured using MitoSOX Red fluorescence, and pyroptosis was evaluated via Hoechst 33342/PI staining. Western blot was used to measure TET2, the NOD-like receptor thermal protein domain associated protein 3 (NLRP3), proteolytic cleavage of gasdermin D (GSDMD), CYTB, and Caspase-1 expression. Interleukin (IL)-1β was quantified by ELISA. The mRNA expression of IL-1β, CYTB, ND2, and TET2 was measured by qRT-PCR. Cellular ultrastructure was examined by electron microscope, and calcium flux was monitored with Fluo-4AM. <i>CYTB</i> methylation was detected using Targeted Bisulfite Sequencing.</p><p><strong>Results: </strong>This study showed that TMAO can down-regulate the expression of CYTB inVECs, cause VECs pyroptosis and mitochondrial dysfunction (MDF). CYTB overexpression antagonized the effect of TMAO. Further, silencing CYTB promoted mtROS production, and MitoTEMPO, a ROS scavenger, inhibited VECs pyroptosis caused by CYTB silencing. In addition, TET2 had demethylation activity. The expression of CYTB was positively regulated by TET2. TMAO was able to inhibit the expression of TET2 and promote the methylation level of the <i>CYTB</i> gene promoter.</p><p><strong>Conclusion: </strong>TMAO promotes the methylation level of the <i>CYTB</i> gene promoter and down-regulates the expression of CYTB by inhibiting the expression of TET2. The decreased expression level of CYTB induces ROS, promoting VECs pyroptosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8719-8733"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575646","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":"Sepsis with Cancer is Marked by a Dysregulated Myeloid Cell Compartment: A Pilot Study.","authors":"Wenqian Qi, Junyan Han, Yu Cao, Hao Yu, Jingjing Hao, Ningning Yin, Xuefeng Zang, Lei Zhao, Wei Chen, Chen Chen, Hui Zeng, Jingyuan Liu, Ang Li","doi":"10.2147/JIR.S523997","DOIUrl":"10.2147/JIR.S523997","url":null,"abstract":"<p><strong>Background: </strong>Sepsis accounts for a significant proportion of global deaths and has limited treatment options. Cancer patients are at a higher risk of sepsis and experience worse outcomes, highlighting the complex interplay between sepsis and cancer on immune cell function and clinical prognosis.</p><p><strong>Methods: </strong>Between July and December 2023, we prospectively enrolled 30 sepsis patients and 10 healthy controls, categorizing the patients into sepsis with non-cancer and sepsis with cancer based on established clinical diagnostics. Multi-color flow cytometry was used to monitor changes in the expression of surface molecules of monocyte and neutrophil subsets, phagocytic activity and cytokine-producing capacity.</p><p><strong>Results: </strong>Compared with sepsis with non-cancer, the sepsis with cancer group demonstrated elevated 28-day mortality rates, increased CD177⁺ activated band neutrophil and HLA-DR^lowCCR2^low classical monocyte, and attenuated phagocytic activity of immature neutrophil and monocyte. Further, HLA-DR^lowCCR2^low classical monocytes and CD177⁺ myelocytes may serve as immunological predictors of adverse outcomes in sepsis. The HLA-DR^lowCCR2^low classical monocyte and CD177⁺ myelocytes exhibit significant correlations with internal environment and coagulation markers.</p><p><strong>Conclusion: </strong>In septic patients, particularly those patients with cancer, attenuated phagocytic activity of immature neutrophil (myelocytes, metamyelocytes, band neutrophils) and monocyte, and HLA-DR^lowCCR2^low classical monocyte and CD177⁺ myelocytes may serve as immunological predictors of poor prognosis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8643-8656"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584140","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":"Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest.","authors":"Yuan Qin, Gangguo Ma, Xiao Xiao, Yongfei Liu, Zhaoyan Zhao, Fang Zhao, Fei Guo, Shuang Wang, Xude Sun, Changjun Gao","doi":"10.2147/JIR.S525373","DOIUrl":"10.2147/JIR.S525373","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a critical element to cardiac arrest (CA)-induced global cerebral ischemia injury. Electroacupuncture (EA) treatment has demonstrated therapeutic potentials in both animal and clinical studies for the cerebral ischemic treatment. Nevertheless, the neuroprotective effect of electroacupuncture at ST36 (EA-ST36) in CA-induced global cerebral ischemia injury and the underlying mechanisms remains unclear.</p><p><strong>Methods: </strong>Using a rat model of Asphyxial Cardiac Arrest, the neuroprotective effects of EA-ST36 were evaluated. Single cell RNA-seq analyses were performed to assess the genetic expression of pyroptosis in different cell types of brain. Cognitive performance was tested through the Morris water maze, while neuronal survival, microglial pyroptosis, and neuroinflammation were analyzed by immunofluorescence, flow cytometry, ELISA, and histopathological staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary microglia was established to confirm the role of α7nAChR in inhibiting pyroptosis.</p><p><strong>Results: </strong>Single-cell RNA sequencing of rat brain and immunofluorescent co-localization showed that pyroptosis is principally occurred in microglia rather than neurons, astrocytes, oligodendrocytes, or endothelial cells in CA/CPR rats. EA-ST36 treatment significantly improved spatial learning and memory in CA/CPR rats, reduced neuronal loss, and attenuated neuroinflammation. These neuroprotective effects were associated with suppressed microglial pyroptosis and decreased IL-1β and IL-18 levels. Remarkably, these neuroprotective effects were abolished by α7nAChR inhibitors. In vitro, α7nAChR activation suppressed OGD/R-induced microglial pyroptosis by inhibiting expression of NLRP3, cleaved caspase-1, and N-GSDMD, and decreased IL-1β and IL-18 levels and alleviated the neurotoxic effects of pyroptotic microglia.</p><p><strong>Conclusion: </strong>Our study revealed that EA-ST36 exerted neuroprotective effects with a potent anti-neuroinflammatory potential by suppressing microglial pyroptosis in a rat CA/CPR model, and these anti-neuroinflammatory properties are α7nAChR-dependent.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8705-8718"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575640","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":"Immune Cell Characteristics in a Gut-Kidney Axis-Induced Mouse Model of IgA Nephropathy: The Upregulated Dendritic Cells and Neutrophils.","authors":"Jiaqi Liu, Yuna Chen, Qijun Wan","doi":"10.2147/JIR.S519521","DOIUrl":"10.2147/JIR.S519521","url":null,"abstract":"<p><strong>Background: </strong>IgA nephropathy (IgAN) is the leading type of primary glomerulonephritis, significantly contributing to chronic kidney disease (CKD) and renal failure. The pathogenesis of IgAN is the multi-hit hypothesis regarding overproduction and accumulation of galactose-deficient (Gd-IgA1). Recent findings have revealed gut microbiota dysbiosis and immune responses are essential in the development of IgAN, attracting increasing attention. This study aimed to map mucosal immune cells in IgAN influenced by gut microbiota, investigating the role of innate immune cells in kidney damage.</p><p><strong>Methods: </strong>Fecal samples were acquired from both patients and controls for subsequent animal experiments. Mice received a broad-spectrum antibiotic cocktail to eliminate their intestinal microflora, followed by a gavage with fecal microbiota from clinical individuals. Murine intestinal and kidney tissues were collected for flow cytometry. Intestine and kidney histopathology, immunofluorescence, and inflammatory cytokine expression were assessed in the murine models. The mucosal epithelium's structure and function, along with the innate immune cell response, were analyzed.</p><p><strong>Results: </strong>Mice exhibited the IgAN phenotype following colonization with gut microbiota from IgAN patients. These mice (IgAN-FMT mice) showed renal dysfunction and increased pathology of tissue injury in both intestine and kidneys. IgAN-FMT mice showed heightened pro-inflammatory cytokine (IL-6 and TNF-α) activity, greater antibody (IgA and complement C3) deposition and decreased expression of mucosal barrier protein (ZO-1, Occludin) compared to the control group. Furthermore, CD11c⁺dendritic cells were more abundant in the murine intestine and kidneys compared to the control group.</p><p><strong>Conclusion: </strong>The gut-kidney axis, including microbiota homeostasis and innate immune cell response, contributes to the pathogenesis of IgAN. Gut dysbiosis and hyperactivated immune cells like CD11c⁺dendritic cells can affect the mucosal barrier and exacerbate the renal damage, being novel insights into immunotherapeutic strategies for IgAN.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8579-8592"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575641","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 Role of EZH2 in Initiating Epigenetic Regulation of CRSwNP.","authors":"Rong Zeng, Yakun Wang, Xinyu Song, Jianting Wang","doi":"10.2147/JIR.S525688","DOIUrl":"10.2147/JIR.S525688","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) was a polygenic disease whose pathogenesis involved epigenetic mechanisms. This study aimed to analyze biomarkers and pathways associated with CRSwNP using RNA-sequencing and explore the role of key biomarkers in the inflammatory response through epigenetic regulation in nasal mucosal cells. Particularly on EZH2, a key epigenetic regulator and histone methyltransferase, to explore its potential for CRSwNP immunotherapy.</p><p><strong>Patients and methods: </strong>A total of 86 individuals were included between July 2021 and July 2023, including 43 patients with CRSwNP who underwent nasal polyp surgery and 43 patients with a deviated septum. Initially, differentially expressed genes (DEGs) between CRSwNP and control groups were screened using the obtained transcriptomic sequencing CRSwNP dataset. Biomarkers were filtered using machine learning algorithms and validated using immunohistochemistry (IHC) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression of enhancer of zeste homolog 2 (EZH2) was knocked down via siRNA and overexpressed through plasmid transfection in human nasal epithelial cells (HNEpCs). The effects of EZH2 overexpression and knockdown on the expression of high-mobility gene group A2 (HMGA2) activation and H3k27me3 expression were assessed using qRT-PCR and immunofluorescence.</p><p><strong>Results: </strong>EZH2, insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and HMGA2 were revealed as potential biomarkers which screened from five target genes. Gene set enrichment analysis and immune infiltration analysis revealed the most critical gene was EZH2, with its expression exhibiting a positive relationship with HMGA2. Moreover, EZH2 knockdown upregulated H3k27me3 expression and inhibited HMGA2 activation. In contrast, EZH2 overexpression downregulated H3k27me3 expression and promoted HMGA2 activation. Notably, the expression levels of IGF2BP1, EZH2, and HMGA2 were higher in the CRSwNP group than in the control group.</p><p><strong>Conclusion: </strong>This study identified three potential biomarkers, IGF2BP1, EZH2, and HMGA2, associated with CRSwNP. Notably, EZH2 could serve as a new adjuvant immunotherapy target in CRSwNP through the modulation of epigenetic mechanisms.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8607-8628"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584142","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":"Amentoflavone Impedes NF-κB Activation and Mediates Apoptosis Induction in Lung Cancer Cells: An in vitro and in silico exploration.","authors":"Syed Shah Mohammed Faiyaz, Afza Ahmad, Daniya Fatima, Syed Monowar Alam Shahid, Gaurav Kaushik, Chaitenya Verma, Rohit Kumar Tiwari, Vinay Kumar","doi":"10.2147/JIR.S521756","DOIUrl":"10.2147/JIR.S521756","url":null,"abstract":"<p><strong>Context: </strong>Lung carcinoma is a major contributor to cancer incidence and mortality worldwide. Chronic activation of NF-κB triggers activation of its target genes involved in promoting malignancy, metastasis, irregular proliferation of cells, and/or their resistance to programmed cell death. Amentoflavone (AMF) is a biflavonoid with intrinsic ability to modulate key signaling pathways associated with homeostatic and non-homeostatic conditions impels its exploration as therapeutic candidate against non-small cell lung carcinoma (NSCLC) A549 cells.</p><p><strong>Objective: </strong>This study investigates the anticancer potential of AMF in A549 cells, focusing on its unique dual role in NF-κB suppression and apoptosis induction, and compares its efficacy to the standard drug doxorubicin.</p><p><strong>Materials and methods: </strong>A549 cells were treated with varying concentrations of AMF for 24 h. The effects of AMF on cell proliferation, oxidative stress, mitochondrial membrane potential, caspase activation, apoptosis, and NF-κB activation was analyzed.</p><p><strong>Results: </strong>A549 cell viability was substantially reduced (P < 0.001) at an AMF concentration of 60 µM. AMF exposure further increased nuclear fragmentation and condensation in A549 cells. AMF treatment induced apoptosis with concomitant augmentation intracellular production of reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and activation of the caspase cascade. Additionally, AMF mediated the inhibition of NF-κB and modulated the expression of NF-κB-associated genes involved in cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclinD1). These results were further supported by in silico studies, which demonstrated a considerable binding energy score of AMF with NF-κB p65/50 compared with the standard drug (doxorubicin).</p><p><strong>Conclusion: </strong>Thus, it was concluded that AMF exerts potent anticancer effects in NSCLC A549 cells through dual mechanism such as direct inhibition of NF-κB signaling and apoptosis induction combined with its high binding affinity, positions it as a promising therapeutic candidate for NSCLC. Further preclinical studies are warranted to validate these findings.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8657-8673"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575639","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":"Developing an Interpretable Machine Learning Model for Early Prediction of Cardiovascular Involvement in Systemic Lupus Erythematosus.","authors":"Zixian Deng, Huadong Liu, Feng Chen, Qiyun Liu, Xiaoyu Wang, Caiping Wang, Chuangye Lyu, Jianghua Li, Tangzhiming Li","doi":"10.2147/JIR.S526608","DOIUrl":"10.2147/JIR.S526608","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease is a leading cause of death in systemic lupus erythematosus (SLE). Early prediction of cardiac involvement is critical for improving patient outcomes. This study aimed to identify key factors associated with cardiac involvement in SLE and to develop an interpretable machine learning (ML) model for risk prediction.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 1,023 SLE patients hospitalized in Shenzhen People's Hospital between January 2000 and December 2021, with a median age of 31 years at hospitalization (IQR: 25-39 years), 92.1% being female, and 18.77% developing cardiovascular involvement during a median follow-up of 3,737 days (IQR: 1,920-5,246). The most predictive features were selected through the intersection of three feature selection techniques: Random Forest, LASSO, and XGBoost. Models were trained on 70% of the dataset and tested on the remaining 30%. Among seven evaluated algorithms, the Gradient Boosting Machine (GBM) demonstrated the best performance on the test set. Model interpretability was assessed using the DALEX package, which generated feature importance plots and instance-level breakdown profiles to visualize decision-making logic.</p><p><strong>Results: </strong>Over a median follow-up of 3737 days, 192 (18.77%) patients developed cardiac involvement. Seven key predictors-arthritis, hypertension, HDL-C, LDL-C, total cholesterol, CRP, and ESR- were identified from 51 clinical and biological variables at admission. The Gradient Boosting Machine (GBM) model (AUC: 0.748, Accuracy: 0.779, Precision: 0.605, F1 score: 0.433, recall 0.338) performed the best of the seven models.</p><p><strong>Conclusion: </strong>This study is the first to develop an interpretable ML model to predict the risk of cardiac involvement in SLE. Notably, the GBM model showed optimal performance, and its interpretability allowed clinicians to visualize decision-making processes, facilitating early identification of high-risk patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8629-8641"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584138","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 Role of Type 2 Innate Lymphoid Cells in Adenoid Hypertrophy with Allergic Rhinitis Among Children and Related Potential Therapeutic Targets.","authors":"Yan Hao, Tian-Yong Hu, Mei-Zhen Zhao, Xian-Hai Zeng, Ke Li, Bao-Hui Cheng, Da-Bo Liu","doi":"10.2147/JIR.S515707","DOIUrl":"10.2147/JIR.S515707","url":null,"abstract":"<p><strong>Objective: </strong>Innate lymphoid cells (ILC) are a heterogeneous group of immune cells implicated in immune diseases. However, their specific roles in adenoid hypertrophy (AH), AH with allergic rhinitis (AH+AR), and AH with otitis media with effusion (AH+OME) remain poorly understood. This study aimed to characterize ILC subsets and their association with immunological profiles in these conditions.</p><p><strong>Methods: </strong>Flow cytometry was used to quantify ILC subsets in adenoid tissues from patients with AH, AH+AR, or AH+OME, and correlations between ILC subsets and clinical, immunological (serum and tissue cytokines), and histopathological parameters were further assessed.</p><p><strong>Results: </strong>ST2 mRNA and protein expression were significantly higher in AH+AR than in AH and AH+OME (p < 0.05). Serum IL-33 was elevated in AH+AR compared to AH (p = 0.0127), while IFN-γ was higher in AH than in AH+AR (p = 0.0044). IL-4 levels were higher in AH and AH+AR than in AH+OME (p < 0.005). Flow cytometry showed that ILC2 predominated in AH+AR (p = 0.0009 vs AH+OME), with higher ILC2/ILC1 and ILC2/ILC3 ratios in AH and AH+AR compared to AH+OME (p < 0.05). Correlation analysis indicated that ILC2 in AH+AR positively correlated with serum IgE, IL-4, IL-33, thymic stromal lymphopoietin (TSLP), and tissue IL-4, IL-33, TSLP, and IL-25 (p < 0.05). ILC3 inversely correlated with peripheral blood eosinophils (p = 0.0125) and positively with serum and tissue IL-17A (p < 0.05).</p><p><strong>Conclusion: </strong>ILC2 cells are significantly enriched in adenoid tissues of patients with AH+AR, with elevated ST2 and IL-33 levels supporting the activation of the IL-33/ST2/ILC2 signaling pathway. Targeting this pathway may offer novel therapeutic strategies for AH combined with allergic rhinitis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8593-8605"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575645","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":"Mechanisms and Factors Influencing Resorption of Herniated Part of Lumbar Disc Herniation: Comprehensive Review.","authors":"Qilong Lai, Guanyi Gong, Yukai Lu, Peijie You, Yicheng Zhu, Zhiqiang Wang, Shun Lin, Hong Jiang, Xiaochun Li, Jintao Liu","doi":"10.2147/JIR.S525233","DOIUrl":"10.2147/JIR.S525233","url":null,"abstract":"<p><strong>Abstract: </strong>This review systematically examines the mechanisms underlying the spontaneous resorption of lumbar disc herniation (LDH), focusing on vascularization, autophagy, apoptosis, macrophage activity, and the therapeutic potential of traditional Chinese medicine (TCM). We emphasize that resorption is influenced by factors such as herniation type, disease duration, and imaging biomarkers (eg, the bull's-eye sign). Additionally, this review summarizes recent progress in the study of resorption mechanisms following lumbar disc herniation, providing a reference for future clinical research.</p><p><strong>Methods: </strong>Literature was systematically searched in PubMed, Web of Science, and CNKI (2000-2024) using keywords: 'lumbar disc herniation,' 'resorption,' 'autophagy,' 'TCM.' Inclusion criteria: (1) human/animal studies; (2) MRI-confirmed LDH; (3) English/Chinese full texts. Exclusion criteria: case reports (n<10).</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8553-8562"},"PeriodicalIF":4.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575642","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":"Reduced Thioredoxin Regulates IL-1β Secretion via NLRP3 of IL-1β+ Alveolar Macrophages in COPD.","authors":"Lueli Wang, Rui Shi, Zhaoliang Li, Ruoqiu Ma, Chongyu Wang, Changli Xu, Rong Guo, Chuang Xiao, Xiaohua Du, Weimin Yang","doi":"10.2147/JIR.S513004","DOIUrl":"10.2147/JIR.S513004","url":null,"abstract":"<p><strong>Objective: </strong>Chronic obstructive pulmonary disease (COPD) is a disease with a complex etiology. The secretion of inflammatory factors, such as IL-1β and oxidative stress, plays an important role in the pathogenesis of COPD. The aim of this paper is to investigate the changes in the redox protein thioredoxin (TRX) in COPD and the role TRX plays in IL-1β release.</p><p><strong>Methods: </strong>We analyzed data from single-cell RNA sequencing (scRNA-seq) of COPD lung tissue in the GEO database. Changes in TRX expression levels and activity were assessed by protein activity analysis of alveolar macrophages(AM). Using Monocle2 and molecular dynamics(MD) to analyze which pathways through TRX achieves regulation of the inflammatory response. The analytical results were subsequently validated by constructing vivo and vitro models.</p><p><strong>Results: </strong>AM that specifically synthesize IL-1β were identified by scRNA-seq. No change in TRX expression levels and decreased protein antioxidant activity in IL-1β+ AM with COPD. We confirmed an increase in oxidized TRX (oxTRX) and a decrease in reduced TRX (reTRX) in COPD mouse model and THP-1 cell model. The decrease in reTRX was accompanied by the upregulation of NLRP3 activity, which played a catalytic role in the synthesis of IL-1β in this subgroup. This was subsequently confirmed in a cigarette smoke-induced THP-1 cell model. A decrease in reTRX level accompanied by an upregulation of NLRP3 activity, which plays a facilitating role in the synthesis of IL-1β. We determined that reTRX reduction was followed by depolymerization of thioredoxin-interacting protein (TXNIP) through MD and immune co-precipitation (CO-IP). Then TNXIP interacted with NLRP3 and up-regulate NLRP3 activity, which in turn promoted IL-1β release.</p><p><strong>Conclusion: </strong>Our study shows that the reTRX is abnormally altered in COPD and leads to the upregulation of NLRP3 activity in AM to enhance IL-1β production.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8563-8578"},"PeriodicalIF":4.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575643","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}