{"title":"Clonorchis sinensis Infection prevents DSS-induced Colitis Via Lithocholic Acid in a Gut Microbiota-Dependent Manner.","authors":"Beibei Zhang, Na Xu, Zheng-Rui Bian, Chen Zhang, Xing Li, Xin-Xin Ren, Zhihua Jiang, Zhongdao Wu, Qian Yu, Kui-Yang Zheng, Mu-Xin Chen, Chao Yan","doi":"10.1007/s10753-025-02241-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02241-4","url":null,"abstract":"<p><p>Increasing evidence demonstrates that helminth and its components can ameliorate ulcerative colitis. Clonorchis sinensis (C. sinensis) is a kind of helminth that dwells in the bile ducts for many years, but the roles and underlying mechanisms of C. sinensis-induced protection from colitis are not elucidated. In the present study, the mice were infected with 50 C. sinensis metacercariae and further administrated with 4% Dextran Sodium Sulfate (DSS) in drinking water for 7 days on days 49 post-infection. The disease severity and the integrity of gut barriers were evaluated. Gut microbiota was measured using 16sRNA sequencing, and bile acids in the colon were detected by Liquid Chromatography Mass Spectrometry (LC/MS). The Co-housing approach or microbiota deletion with additional supplies of secondary bile acids (SBAs) was employed to investigate the roles of gut microbiota in the protection from colitis. C. sinensis infection moderated the dysbiosis of the intestinal microbiota and increased the levels of SBAs and bile acid receptor Takeda G protein-coupled receptor 5 (TGR5), which finally benefited anti-inflammation and ameliorated the severity of DSS-induced colitis. Co-housing with C. sinensis-infected mice, and non-infected mice with colitis also showed an increase of TGR5, decreased pro-inflammatory cytokines, and a reduction in the severity of colitis, compared to those mice suffering from colitis without co-housing. Furthermore, C. sinensis-induced protective effects on colitis were attenuated by microbiota deletion, while SBAs (lithocholic acid, LCA) supplementation reversed the colitis. The present study demonstrates that C. sinensis infection ameliorates DSS-induced ulcerative colitis in mice, which is dependent on gut microbiota-associated SBAs.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microbiological and Metabolomic Analysis of Biomarkers for Grades A and B in Stage II Periodontitis.","authors":"Wenjie Dai, Yuhan Ye, Bingyong Mao, Xin Tang, Shumao Cui, Jianxin Zhao, Chenchen Feng, Qiuxiang Zhang","doi":"10.1007/s10753-025-02260-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02260-1","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease characterized by inflammation of the periodontal soft tissues and loss of alveolar bone. In the oral environment, subgingival microorganisms and salivary metabolites reflect the host's health status. This study aimed to understand periodontitis severity and progression rate by analyzing subgingival microflora and salivary metabolites to identify potential biomarkers. Fifty-three volunteers with stage II periodontitis were graded using the bone loss (%)/age index into two grades: 33 in grade A (< 0.25) and 20 in grade B (0.25-1.00). Using a case-control study, simultaneously analyzed biomarkers associated with the severity and rate of progression of periodontitis. The red complex, the orange complex, Campylobacter spp., uncultured Candidatus Saccharibacteria and metabolites such as 5-Aminovaleric acid, N1-Acetylspermine showed a significant positive correlation with periodontal clinical parameters. Furthermore, we identified four of the salivary differential metabolites (DL-Leucineamide, Dodecanedioic acid, L-Tyrosine methyl ester and Phenylpyruvic acid) that may serve as potential biomarkers for predicting the rate of periodontitis progression. These results showed that the red complex significantly correlated with periodontitis severity and influenced changes in salivary metabolites. Additionally, biomarkers indicating the progression rate were predominantly amino acid derivatives, confirming that interactions between microorganisms and metabolites may exacerbate periodontitis development.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FDA-Approved Secukinumab Alleviates Glial Activation and Immune Cell Infiltration in MPTP-Induced Mouse Model of Parkinson's Disease.","authors":"Qi Li, Xiaoxuan Han, Mengmeng Dong, Lipeng Bai, Wei Zhang, Wei Liu, Fei Wang, Xiaodong Zhu","doi":"10.1007/s10753-025-02267-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02267-8","url":null,"abstract":"<p><p>Interleukin-17A (IL-17A) has been implicated in the progression of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the effect of the FDA-approved Secukinumab (SEC), an IL-17A inhibitor, on PD remains unclear. This study aimed to investigate the neuroprotective effect of SEC and its potential mechanisms in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Male C57BL/6 J mice were mainly assigned to three groups: Sham, MPTP, and MPTP + SEC. Motor coordination was assessed using the climbing rod and rotarod tests. Dopaminergic neurons (TH +) and glial cells (Iba-1 + , GFAP +) in the substantia nigra were evaluated using immunohistochemistry and immunofluorescence. Flow cytometry was used to analyze immune cell populations in the brain and spleen. Inflammatory cytokines and chemokines were quantified using RT-PCR. SEC treatment significantly alleviated the loss of dopaminergic neurons and improved motor coordination in MPTP mice. It also reduced the infiltration of peripheral immune cells, including CD4 + T cells, NK cells, and monocyte-macrophages into the brain. SEC attenuated glial activation (Iba-1 + , GFAP +) and decreased the expression of pro-inflammatory cytokines and chemokines (CCL2, CXCL9), which recruit immune cells into the brain. These results suggest that Secukinumab protects dopaminergic neurons and attenuates neuroinflammation in MPTP-induced model. SEC treatment in PD might be an effective therapeutic approach for clinical application in the future. HIGHLIGHTS: • Secukinumab reduces the loss of dopaminergic neurons and axons in MPTP mice. • Secukinumab inhibits the infiltration of peripheral immune cells into the brain in MPTP mice. • Secukinumab inhibits the activation of glial cells and reduces neuroinflammation in MPTP mice.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ZAKα Induces Pyroptosis of Colonic Epithelium Via the Caspase-11/GSDMD Pathway to Aggravate Colitis.","authors":"Song Li, Mingfei Chen, Sizhe Zheng, Waresi Abudourexiti, Feng Zhu, Zhongyuan Wang, Yanzhe Guo, Zeqian Yu, Zirui Yang, Liang Zhang, Chao Ding, Jianfeng Gong","doi":"10.1007/s10753-025-02262-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02262-z","url":null,"abstract":"<p><p>ZAKα-driven ribotoxic stress response (RSR) has been shown to trigger diverse biological effects. Nevertheless, its role in the pathogenesis of ulcerative colitis (UC) remained unclear. This study aimed to determine the role of ZAKα in the development of UC. Our study found that ZAKα expression was significantly increased in colonic epithelium of UC patients and DSS-colitis mouse models. Moreover, the expression level of ZAKα mRNA showed a positive correlation with disease activity. In the colitis model, Vemurafenib, the ZAKα inhibitor, treatment reduced colonic inflammation and ameliorated intestinal mucosal barrier damage, while Anisomycin, the RSR agonist, showed the opposite effect. In vitro experiments demonstrated that Anisomycin induced pyroptosis instead of apoptosis in C26 cell line. Western blot analysis revealed that Anisomycin triggered pyroptosis via the Caspase-11/GSDMD pathway. Further animal studies confirmed that Vemurafenib downregulated this pathway, reducing colonic epithelial cell pyroptosis. Finally, blocking Caspase-11 reduced severity of DSS-induced colitis in Anisomycin-treated mice. In all, ZAKα seems to play a crucial role in the pathogenesis of colitis, as it promotes pyroptosis in colonic epithelial cells and exacerbates colitis in part by upregulating the Caspase-11/GSDMD axis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InflammationPub Date : 2025-02-24DOI: 10.1007/s10753-025-02265-w
Na Guo, Yu Xia, Nannan He, Lei Zhang, Jian Liu
{"title":"IRGM Inhibits the AKT/mTOR Signaling Pathway by Interacting with TRIM21 to Alleviate Sepsis-Induced Acute Lung Injury.","authors":"Na Guo, Yu Xia, Nannan He, Lei Zhang, Jian Liu","doi":"10.1007/s10753-025-02265-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02265-w","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a severe complication of sepsis, and its underlying pathological mechanisms remain poorly understood. This study aims to investigate the role and mechanisms by which IRGM mediates autophagy through the regulation of the AKT/mTOR signaling pathway in sepsis-induced ALI. Initially, a sepsis-induced ALI mouse model was established using cecal ligation and puncture (CLP). Our results demonstrated that Irgm1 expression was significantly upregulated in the ALI model. Subsequently, Irgm1 was knocked down in vivo using AAV vectors, and changes in ALI symptoms were assessed. In vitro, a sepsis-induced ALI cell model was generated by stimulating A549 cells with lipopolysaccharide (LPS). The effects of IRGM overexpression on autophagy and apoptosis were evaluated, and its impact on the AKT/mTOR signaling pathway was analyzed. Furthermore, mass spectrometry and co-immunoprecipitation (COIP) experiments were conducted to explore the interaction between IRGM and TRIM21. In vivo results showed that Irgm1 knockout exacerbated CLP-induced ALI, as evidenced by a significant reduction in autophagic activity, increased apoptosis, and aberrant activation of the AKT/mTOR pathway. Further cellular experiments suggested that IRGM may enhance autophagy by inhibiting the AKT/mTOR signaling pathway, thereby attenuating LPS-induced cell damage. Additionally, COIP experiments revealed that IRGM interacts with TRIM21 to inhibit AKT/mTOR pathway activation, thereby promoting autophagy and mitigating sepsis-induced ALI. In conclusion, IRGM regulates autophagy through the AKT/mTOR signaling pathway and exerts protective effects in sepsis-induced ALI, suggesting that it may serve as a potential therapeutic target for sepsis-related ALI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InflammationPub Date : 2025-02-22DOI: 10.1007/s10753-025-02268-7
You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li
{"title":"4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway.","authors":"You Li, Yang Li, Pengfei Li, Lei Yang, Haijun Li","doi":"10.1007/s10753-025-02268-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02268-7","url":null,"abstract":"<p><p>Bone marrow mesenchymal stem cells (BMSCs) play an important role in bone metabolism and tissue repair, and their ability to differentiate into osteoblasts is crucial in the treatment of bone diseases such as postmenopausal osteoporosis (PMOP). However, the function of BMSCs may be affected by ferroptosis. Ferroptosis is a cell death mode characterized by excess Fe<sup>2+</sup> and lipid peroxidation, which significantly affects the survival rate and differentiation ability of BMSCs. This study investigated the effect of exogenous itaconate derivative 4-octyl itaconate (4-OI) on Erastin-induced BMSCs ferroptosis. The results showed that 4-OI significantly inhibited Erastin-induced BMSCs ferroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, reduced reactive oxygen species levels and oxidative damage, and restored antioxidant capacity. At the same time, 4-OI promoted the osteogenic differentiation of BMSCs. Further experiments showed that Nrf2-IN-1, an inhibitor of the Nrf2 pathway, could reverse the protective effect of 4-OI. In vivo, 4-OI was shown to reduce bone loss in ovariectomized (OVX) mice, as assessed by Micro-CT analysis. Immunofluorescence staining further revealed increased GPX4 and Nrf2 expression in vertebral tissues following 4-OI treatment. These results indicate that 4-OI improves ferroptosis of BMSCs and enhances osteogenic differentiation ability by activating the Nrf2 pathway, providing new research ideas and potential targets for the treatment of PMOP.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InflammationPub Date : 2025-02-21DOI: 10.1007/s10753-025-02263-y
Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li
{"title":"High-Resolution Untargeted Metabolomics Reveals Alternate-Day Fasting May Attenuate Diabetic Kidney Disease Progression in BTBR ob/ob Mice by Affecting the HCA, IPA and Reducing Inflammation.","authors":"Huiqing Yu, Liping Yan, Jiaqing Ma, Xinduo Zhang, Hongman Wu, Yahui Yan, Hong Shen, Zhiguo Li","doi":"10.1007/s10753-025-02263-y","DOIUrl":"https://doi.org/10.1007/s10753-025-02263-y","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most severe complications of diabetes mellitus, with limited effective therapeutic interventions. Alternate-day fasting (ADF) shows potential in treating DKD, though its mechanisms are not fully understood. In this study, BTBR ob/ob mice underwent 12 weeks of ADF, and high-resolution untargeted metabolomics were performed to uncover the underlying mechanisms. After 12 weeks of ADF, the BTBR ob/ob mice exhibited weight loss, lower blood glucose and LDL-C levels, reduced 24-h urinary protein excretion, and decreased renal collagen deposition. A total of 44 metabolites were differentially expressed, with 25 up-regulated and 19 down-regulated. Notably, hyocholic acid (HCA) and indole-3-propionic acid (IPA), both products of intestinal bacteria, can modulating inflammation were differentially expressed. Furthermore, the kidneys of BTBR ob/ob mice showed significantly lower NF-κB pathway activity and reduced inflammation after 12 weeks of ADF. This study indicates that ADF may alleviate DKD progression by modulating HCA, IPA, and decreasing inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InflammationPub Date : 2025-02-21DOI: 10.1007/s10753-025-02269-6
Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert
{"title":"The Vitamin E Derivative Garcinoic Acid Suppresses NLRP3 Inflammasome Activation and Pyroptosis in Murine Macrophages.","authors":"Lisa Börmel, Anja R Geisler, Yvonne Hupfer, Sijia Liao, Tina Schubert, Stefan Kluge, Stefan Lorkowski, Maria Wallert","doi":"10.1007/s10753-025-02269-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02269-6","url":null,"abstract":"<p><p>Excessive inflammation in cells are a common cause of inflammation-related diseases such as cardiometabolic diseases. The cellular multiprotein complex nucleotide-binding domain and leucine-rich repeat pyrin domain 3 (NLRP3) inflammasome is a cellular key modulator of inflammatory processes. In addition to classic medications, phytochemicals are known for their anti-inflammatory potential. In African folk medicine the seeds of Garcinia kola are used to support the treatment of inflammatory diseases. Of particular interest is the phytochemical garcinoic acid (GA, trans-13'-carboxy-δ-tocotrienol), which is isolated from the Garcinia kola seeds. This derivative and potential metabolite of the vitamin E congener δ-tocotrienol (T3) shows anti-inflammatory properties in vitro. However, the underlying mechanisms are largely unknown. To get better insights into the molecular mode of action, murine J774A.1 macrophages were stimulated with lipopolysaccharides (LPS) only or in combination with adenosine triphosphate (ATP), which led to canonical activation of the NLRP3 inflammasome and subsequent pyroptosis. A combined treatment with GA resulted in significantly reduced stimulation of the transcription factor nuclear factor 'ĸ-light-chain-enhancer' of activated B-cells (NF-ĸB), decreased expression of inflammasome-related genes and marked downregulation of autoproteolytic cleavage of caspase-1 (Casp-1). Consequently, GA had an inhibitory effect on pyroptosis. The results have been validated using the well-known NLRP3 inflammasome inhibitor MCC950. In conclusion, GA was shown to have relevant effects on the regulation of the NLRP3 inflammasome and pyroptosis in vitro. Our study provides new mechanistic insights into the anti-inflammatory mode of action of GA and highlights its relevance as a potential phytochemical drug for the treatment of inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis.","authors":"Xiaoyu Zi, Huanhuan Yan, Baochen Li, Chong Gao, Xiaofeng Li, Jing Luo, Caihong Wang","doi":"10.1007/s10753-025-02248-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02248-x","url":null,"abstract":"<p><p>Aberrant number and/or dysfunction of regulatory T cells (Tregs) is associated with the development of rheumatoid arthritis (RA). This study aimed to assess the frequencies of naive Tregs (nTregs) and memory Tregs (mTregs) in the peripheral blood of RA patients and to explore their relationships with cytokine levels. This study involved 97 RA patients categorized into three groups based on Disease Activity Score 28 (DAS28) and 50 healthy controls (HCs). Flow cytometry was employed to quantify Treg subsets in peripheral blood, while serum cytokine concentrations were measured using a flow cytometry bead array. The findings revealed that three RA groups, stratified by disease activity, all exhibited a significant decrease in both the count and percentage of nTregs and an increase in the percentage of mTregs compared to HCs. Notably, the group with high RA disease activity displayed a higher percentage of mTregs than the remission group. Additionally, correlation analysis indicated that IL-2 concentrations were negatively correlated with total T, CD4 + T and Th17 cell counts, and positively correlated with the absolute count of nTregs. This study demonstrated that the count of mTregs in RA patients increased with escalating disease activity, while the count of nTregs remained unchanged. Moreover, IL-2 concentrations were positively correlated with the numbers of Tregs and nTregs, suggesting that IL-2 plays a significant role in modulating Treg subsets. Further studies on targeted therapies aligned with the distribution of mTregs and nTregs in RA patients with varying disease activity could potentially achieve effective remission.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InflammationPub Date : 2025-02-19DOI: 10.1007/s10753-025-02270-z
Congkuan Song, Qingqing Li, Jinjin Zhang, Weidong Hu
{"title":"Uridine Phosphorylase 1 as a Biomarker Associated with Glycolysis in Acute Lung Injury.","authors":"Congkuan Song, Qingqing Li, Jinjin Zhang, Weidong Hu","doi":"10.1007/s10753-025-02270-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02270-z","url":null,"abstract":"<p><p>The specific pathogenesis of acute lung injury (ALI) is complex and not yet clear, and the clinical treatment methods are relatively limited. It is of great clinical significance to explore its pathogenesis and effective molecular targets. Here, we identified an ALI biomarker (UPP1) associated with uridine metabolism by a systematic bioinformatics approach. It was also confirmed to be associated with the glycolytic pathway in the mouse ALI model. In addition, drug sensitivity analysis based on the CMAP database identified three UPP1-associated drugs (CAY10585, XL147 and IOX2) that may be useful in the treatment of ALI. Molecular docking and molecular dynamics simulations further confirmed the stability of the binding between UPP1 and the three drugs. In conclusion, this study confirms that the uridine metabolism gene UPP1 associated with glycolysis is a key biomarker of ALI and provides valuable insights into the potential application of CAY10585, XL147 and IOX2 in ALI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}