Ali-reza Ghasemiyeh, Marzieh Heidarzadeh Arani, Fatemeh Riazian, Ali Aghajani, Mohammad Javad Azadchehr, Hossein Motedayyen
Introduction
Atopic dermatitis (AD), also referred to as atopic eczema, is one of the most common immunological disorders in children. Previous studies have suggested potential roles of interleukin-33 (IL-33) in the onset and progression of AD. This study investigated whether serum IL-33 levels in children with AD are associated with disease severity, immunoglobulin E (IgE) sensitization to food or environmental allergens, and serum IgE concentration.
Methods
The study included 62 children with newly diagnosed AD and 30 age-matched healthy controls. Following an interview and confirmation of disease severity, 3mL of venous blood was collected from each participant. Sensitization to allergens was assessed using a skin prick test. Serum IL-33 (ng/L) and IgE (IU/mL) levels were measured using enzyme-linked immunosorbent assay (ELISA).
Results
Among the 62 children with AD, 51 (82.3%) were sensitized to food allergens, whereas 11 (17.7%) were sensitized to environmental allergens. Most patients (75.8%) had mild AD. Serum IL-33 and IgE levels were significantly elevated in patients compared with healthy controls. Both IL-33 and IgE concentrations were significantly associated with moderate AD. However, IL-33 levels were not correlated with age, gender, or allergen type. Receiver operating characteristic (ROC) analysis revealed that IgE levels demonstrated moderate diagnostic performance for AD (AUCc0.758), while IL-33 showed weaker diagnostic value (AUC = 0.678). For predicting disease severity, IL-33 exhibited strong performance, with the highest sensitivity (85.71%) and maximum specificity (70.21%) at a cut-off of 331.32 ng/L (AUC = 0.862). In contrast, IgE was not a reliable predictor of AD severity.
Conclusion
Serum IL-33 levels are significantly correlated with AD severity and may serve as a predictive biomarker, whereas IgE shows limited utility for severity assessment. Further studies are warranted to validate the clinical applicability of IL-33 in AD management.
{"title":"Predicting Role of Interleukin-33 in Determining the Development and Severity of Atopic Dermatitis","authors":"Ali-reza Ghasemiyeh, Marzieh Heidarzadeh Arani, Fatemeh Riazian, Ali Aghajani, Mohammad Javad Azadchehr, Hossein Motedayyen","doi":"10.1002/iid3.70351","DOIUrl":"https://doi.org/10.1002/iid3.70351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Atopic dermatitis (AD), also referred to as atopic eczema, is one of the most common immunological disorders in children. Previous studies have suggested potential roles of interleukin-33 (IL-33) in the onset and progression of AD. This study investigated whether serum IL-33 levels in children with AD are associated with disease severity, immunoglobulin E (IgE) sensitization to food or environmental allergens, and serum IgE concentration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 62 children with newly diagnosed AD and 30 age-matched healthy controls. Following an interview and confirmation of disease severity, 3mL of venous blood was collected from each participant. Sensitization to allergens was assessed using a skin prick test. Serum IL-33 (ng/L) and IgE (IU/mL) levels were measured using enzyme-linked immunosorbent assay (ELISA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 62 children with AD, 51 (82.3%) were sensitized to food allergens, whereas 11 (17.7%) were sensitized to environmental allergens. Most patients (75.8%) had mild AD. Serum IL-33 and IgE levels were significantly elevated in patients compared with healthy controls. Both IL-33 and IgE concentrations were significantly associated with moderate AD. However, IL-33 levels were not correlated with age, gender, or allergen type. Receiver operating characteristic (ROC) analysis revealed that IgE levels demonstrated moderate diagnostic performance for AD (AUCc0.758), while IL-33 showed weaker diagnostic value (AUC = 0.678). For predicting disease severity, IL-33 exhibited strong performance, with the highest sensitivity (85.71%) and maximum specificity (70.21%) at a cut-off of 331.32 ng/L (AUC = 0.862). In contrast, IgE was not a reliable predictor of AD severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Serum IL-33 levels are significantly correlated with AD severity and may serve as a predictive biomarker, whereas IgE shows limited utility for severity assessment. Further studies are warranted to validate the clinical applicability of IL-33 in AD management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146139452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid deposition in alcoholic fatty liver disease (AFL) represents an early stage in alcoholic liver disease progression and may contribute to carcinogenesis. MicroRNAs (miRNAs) play critical regulatory roles in liver biological processes.
Methods
In this study, we explored the miR-18a-5p/CYP1A1/PPAR axis in AFL using bioinformatics approaches. An AFL rat model was created, and second-generation sequencing identified differentially expressed mRNA in rat liver tissues. Core genes were identified through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Gene Expression Omnibus database analyses. These genes were validated by qPCR in liver tissues and via in vitro experiments using L02 cells. The upstream miRNA identified in AFL was further verified in L02 cells using luciferase reporter assays.
Results
Differential gene analysis revealed CYP1A1 and the PPAR pathway. In alcohol-induced L02 cells, increased CYP1A1 expression promoted oxidative stress and altered lipid metabolism via the PPAR pathway. MiR-18a-5p was identified as an upstream regulator that targets CYP1A1 to ameliorate alcohol-induced oxidative stress. Inhibition of CYP1A1 by miR-18a-5p improved the expression of PPARγ-related genes and decreased PPARα-related gene expression, thereby reducing lipid deposition.
Conclusion
The miR-18a-5p/CYP1A1/PPAR axis is a novel pathway that could be targeted for AFL treatment.
背景：酒精性脂肪性肝病（AFL）的脂质沉积代表了酒精性肝病进展的早期阶段，并可能导致癌变。MicroRNAs （miRNAs）在肝脏生物学过程中起着关键的调节作用。方法：在本研究中，我们利用生物信息学方法探索了miR-18a-5p/CYP1A1/PPAR轴在AFL中的作用。建立AFL大鼠模型，第二代测序鉴定了大鼠肝组织中差异表达的mRNA。通过基因本体（Gene Ontology）、京都基因与基因组百科全书（Kyoto Encyclopedia of genes and Genomes pathway）和Gene Expression Omnibus数据库分析，鉴定核心基因。这些基因在肝组织和L02细胞的体外实验中被qPCR验证。在AFL中鉴定的上游miRNA在L02细胞中进一步通过荧光素酶报告基因实验进行验证。结果：差异基因分析显示CYP1A1与PPAR通路有关。在酒精诱导的L02细胞中，CYP1A1表达的增加通过PPAR途径促进氧化应激和脂质代谢的改变。MiR-18a-5p被鉴定为上游调节因子，靶向CYP1A1改善酒精诱导的氧化应激。miR-18a-5p抑制CYP1A1可提高ppar γ相关基因的表达，降低ppar α相关基因的表达，从而减少脂质沉积。结论：miR-18a-5p/CYP1A1/PPAR轴是AFL治疗的新靶点。
{"title":"MiR-18a-5p Attenuates Oxidative Stress and Inhibits Lipid Accumulation in Alcoholic Fatty Liver by Activating the CYP1A1-PPAR Axis","authors":"XueMei Zhang, Wei Li, Ubaid Ullah, Ning Li, XinYu Geng, JiHan Qi, HongLiang Chen, Xu Zhang, Ying Hu, Lingling Yang, ShiZhu Jin","doi":"10.1002/iid3.70350","DOIUrl":"10.1002/iid3.70350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lipid deposition in alcoholic fatty liver disease (AFL) represents an early stage in alcoholic liver disease progression and may contribute to carcinogenesis. MicroRNAs (miRNAs) play critical regulatory roles in liver biological processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we explored the miR-18a-5p/CYP1A1/PPAR axis in AFL using bioinformatics approaches. An AFL rat model was created, and second-generation sequencing identified differentially expressed mRNA in rat liver tissues. Core genes were identified through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Gene Expression Omnibus database analyses. These genes were validated by qPCR in liver tissues and via in vitro experiments using L02 cells. The upstream miRNA identified in AFL was further verified in L02 cells using luciferase reporter assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Differential gene analysis revealed CYP1A1 and the PPAR pathway. In alcohol-induced L02 cells, increased CYP1A1 expression promoted oxidative stress and altered lipid metabolism via the PPAR pathway. MiR-18a-5p was identified as an upstream regulator that targets CYP1A1 to ameliorate alcohol-induced oxidative stress. Inhibition of CYP1A1 by miR-18a-5p improved the expression of PPARγ-related genes and decreased PPARα-related gene expression, thereby reducing lipid deposition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The miR-18a-5p/CYP1A1/PPAR axis is a novel pathway that could be targeted for AFL treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Periodontitis, a chronic inflammatory disease, represents the primary cause of tooth loss in Chinese adults. Wilms tumor 1-associating protein (WTAP) is a key component of the N6-methyladenosine (m6A) methyltransferase complex, and has an unclear role in periodontitis pathogenesis, particularly concerning its regulatory functions in periodontal ligament stem cells (PDLSCs).
Methods
The target gene was identified through the GES260558 dataset and Genecards database. Gene expression was measured using reverse transcription-quantitative PCR (RT-qPCR) and western blot. Periodontitis-derived PDLSCs (P-PDLSCs) were isolated and identified by alkaline phosphatase (ALP) staining, oil red O staining, and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels, γ-H2AX and SA-β-gal positive cells, and the expression of p53 and p16 were applied to reflect oxidative stress and cell senescence. Osteogenic differentiation was assessed by ALP activity, alizarin red S (ARS) staining, and related gene expression. The m6A-dependent regulation of tumor protein p53 binding protein 1 (TP53BP1) mRNA by WTAP was confirmed using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and Actinomycin D (Act D) assays.
Results
WTAP was identified as a candidate gene that was upregulated in periodontitis gingival tissues. Isolated P-PDLSCs retained normal multilineage differentiation potential. WTAP knockdown significantly reduced senescence and oxidative stress in P-PDLSCs while enhancing osteogenic differentiation. Mechanistically, WTAP mediated the m6A modification of TP53BP1 mRNA, and the effects of WTAP on P-PDLSC senescence, oxidative stress, and osteogenic differentiation were dependent on TP53BP1.
Conclusion
The WTAP/TP53BP1 axis impairs periodontal tissue regeneration by promoting P-PDLSC senescence and suppressing osteogenic differentiation in an m6A-dependent manner, revealing a new cellular-level target for treating periodontitis.
{"title":"WTAP Contributes to Periodontitis Pathogenesis by Promoting PDLSC Senescence and Impairing Osteogenic Differentiation via m6A-Dependent Regulation of TP53BP1","authors":"Menglin Xiong, Tingting Wang, Yuan Liu","doi":"10.1002/iid3.70335","DOIUrl":"10.1002/iid3.70335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Periodontitis, a chronic inflammatory disease, represents the primary cause of tooth loss in Chinese adults. Wilms tumor 1-associating protein (WTAP) is a key component of the N6-methyladenosine (m6A) methyltransferase complex, and has an unclear role in periodontitis pathogenesis, particularly concerning its regulatory functions in periodontal ligament stem cells (PDLSCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The target gene was identified through the GES260558 dataset and Genecards database. Gene expression was measured using reverse transcription-quantitative PCR (RT-qPCR) and western blot. Periodontitis-derived PDLSCs (P-PDLSCs) were isolated and identified by alkaline phosphatase (ALP) staining, oil red O staining, and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels, γ-H2AX and SA-β-gal positive cells, and the expression of p53 and p16 were applied to reflect oxidative stress and cell senescence. Osteogenic differentiation was assessed by ALP activity, alizarin red S (ARS) staining, and related gene expression. The m6A-dependent regulation of tumor protein p53 binding protein 1 (TP53BP1) mRNA by WTAP was confirmed using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and Actinomycin D (Act D) assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WTAP was identified as a candidate gene that was upregulated in periodontitis gingival tissues. Isolated P-PDLSCs retained normal multilineage differentiation potential. WTAP knockdown significantly reduced senescence and oxidative stress in P-PDLSCs while enhancing osteogenic differentiation. Mechanistically, WTAP mediated the m6A modification of TP53BP1 mRNA, and the effects of WTAP on P-PDLSC senescence, oxidative stress, and osteogenic differentiation were dependent on TP53BP1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The WTAP/TP53BP1 axis impairs periodontal tissue regeneration by promoting P-PDLSC senescence and suppressing osteogenic differentiation in an m6A-dependent manner, revealing a new cellular-level target for treating periodontitis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan-Jun Chen, Jing-Wen Chen, Ming-Rong Xie, Rui-Zhen Wang, Yu-Ling Wan, Jie Zeng, Bing-Wu Zhong, Sheng-Qiang Zhou, Fang Liu
Background
Parkinson's disease (PD) is a major neurodegenerative disorder. Some patients show limited response to standard therapies, driving the need for new complementary treatments. Paning I decoction (PNID), a traditional herbal formula, has shown the potential to alleviate PD symptoms, but its exact mechanisms remain unclear.
Methods
We tested PNID in a mouse model of PD induced by a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received different PNID doses to evaluate symptom alleviation. We used behavioral tests and laboratory analyses to study brain changes, including neuron damage assessment, dopamine and tyrosine hydroxylase (TH) measurements, blood–brain barrier (BBB) integrity and microglia evaluation, and inflammatory marker analysis.
Results
PNID treatment alleviated PD symptoms in a dose-dependent manner. High-dose PNID performed similarly to Madopar. Neuron protection: increased dopamine and TH expression. BBB repair: less leakage and fibrinogen accumulation. Regulation of polarization: shifted microglia from M1 to M2 states. Inflammation control: lowered pro-inflammatory factors (IL-6, IL-1β, and TNF-α) while increasing anti-inflammatory factors (IFN-β, IL-10, and IL-4).
Conclusions
PNID may serve as a promising complementary therapy for PD. Benefits may come from the repair of the BBB, reduction of fibrinogen deposition, and decline in neuroinflammation by modulating microglial polarization.
{"title":"Reducing Neuroinflammation via Inhibition of Fibrinogen Deposition and Microglial Activation as an Underlying Mechanism of Paning I Decoction in Ameliorating Parkinson's Disease Symptoms","authors":"Yan-Jun Chen, Jing-Wen Chen, Ming-Rong Xie, Rui-Zhen Wang, Yu-Ling Wan, Jie Zeng, Bing-Wu Zhong, Sheng-Qiang Zhou, Fang Liu","doi":"10.1002/iid3.70310","DOIUrl":"10.1002/iid3.70310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a major neurodegenerative disorder. Some patients show limited response to standard therapies, driving the need for new complementary treatments. Paning I decoction (PNID), a traditional herbal formula, has shown the potential to alleviate PD symptoms, but its exact mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We tested PNID in a mouse model of PD induced by a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received different PNID doses to evaluate symptom alleviation. We used behavioral tests and laboratory analyses to study brain changes, including neuron damage assessment, dopamine and tyrosine hydroxylase (TH) measurements, blood–brain barrier (BBB) integrity and microglia evaluation, and inflammatory marker analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PNID treatment alleviated PD symptoms in a dose-dependent manner. High-dose PNID performed similarly to Madopar. Neuron protection: increased dopamine and TH expression. BBB repair: less leakage and fibrinogen accumulation. Regulation of polarization: shifted microglia from M1 to M2 states. Inflammation control: lowered pro-inflammatory factors (IL-6, IL-1β, and TNF-α) while increasing anti-inflammatory factors (IFN-β, IL-10, and IL-4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PNID may serve as a promising complementary therapy for PD. Benefits may come from the repair of the BBB, reduction of fibrinogen deposition, and decline in neuroinflammation by modulating microglial polarization.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Differentiating between healthy intrauterine pregnancy (HP) and ectopic pregnancy (EP) in early gestation is clinically challenging.
Aim
This study aimed to evaluate the role of the delta neutrophil index (DNI), pan-immun inflammation value (PIV) and other hematologic inflammatory markers in the preliminary diagnosis of tubal EP. To the best of our knowledge, there are no studies in the literature examining the relationship between DNI, PIV and EP.
Materials and Methods
This retrospective study included 120 women diagnosed with tubal EP and 102 women with HP who presented to a tertiary hospital in Turkey between 2019 and 2023. Inclusion criteria were women with confirmed tubal EP or HP who had complete clinical and hematologic data and no chronic diseases, infections, or body mass index (BMI) > 30 kg/m2. The primary outcome was to assess whether DNI, PIV and other complete blood count (CBC) parameters could differentiate EP from HP. Statistical analysis included t-tests, Welch's t-test, χ2 tests, and ROC analysis; p < 0.05 was considered statistically significant.
Results
No significant difference was found in DNI value (p = 0.256). However, white blood cell count (WBC) (p = 0.007), platelet (PLT) (p = 0.001), lymphocyte (p < 0.001), PIV (p = 0.023), systemic immune-inflammation index (SII) (p = 0.016) and basophil (p = 0.005) levels were higher in the EP group, while hemoglobin (HB) levels were lower (p < 0.001).
Conclusion
While DNI was not a significant marker, other hematologic parameters may support early identification of EP, suggesting an underlying inflammatory process.
{"title":"The Role of the Delta Neutrophil Index, Pan-Immune Inflammation Value and Other Hematologic Inflammatory Parameters in the Preliminary Diagnosis of Tubal Ectopic Pregnancy","authors":"Şeyma Nur Karadag, Dilay Gök Korucu","doi":"10.1002/iid3.70349","DOIUrl":"10.1002/iid3.70349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Differentiating between healthy intrauterine pregnancy (HP) and ectopic pregnancy (EP) in early gestation is clinically challenging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to evaluate the role of the delta neutrophil index (DNI), pan-immun inflammation value (PIV) and other hematologic inflammatory markers in the preliminary diagnosis of tubal EP. To the best of our knowledge, there are no studies in the literature examining the relationship between DNI, PIV and EP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective study included 120 women diagnosed with tubal EP and 102 women with HP who presented to a tertiary hospital in Turkey between 2019 and 2023. Inclusion criteria were women with confirmed tubal EP or HP who had complete clinical and hematologic data and no chronic diseases, infections, or body mass index (BMI) > 30 kg/m<sup>2</sup>. The primary outcome was to assess whether DNI, PIV and other complete blood count (CBC) parameters could differentiate EP from HP. Statistical analysis included <i>t</i>-tests, Welch's <i>t</i>-test, <i>χ</i><sup>2</sup> tests, and ROC analysis; <i>p</i> < 0.05 was considered statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant difference was found in DNI value (<i>p</i> = 0.256). However, white blood cell count (WBC) (<i>p</i> = 0.007), platelet (PLT) (<i>p</i> = 0.001), lymphocyte (<i>p</i> < 0.001), PIV (<i>p</i> = 0.023), systemic immune-inflammation index (SII) (<i>p</i> = 0.016) and basophil (<i>p</i> = 0.005) levels were higher in the EP group, while hemoglobin (HB) levels were lower (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While DNI was not a significant marker, other hematologic parameters may support early identification of EP, suggesting an underlying inflammatory process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ville A. Palomäki, Juha P. Väyrynen, Vesa Koivukangas, Sanna Meriläinen, Tuomo J. Karttunen, Petri Lehenkari
Background
Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity.
Methods
Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up.
Results
Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures.
Conclusions
Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.
{"title":"NLRP3-Caspase-1 Axis in Human Adipose Tissue Crown-Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery","authors":"Ville A. Palomäki, Juha P. Väyrynen, Vesa Koivukangas, Sanna Meriläinen, Tuomo J. Karttunen, Petri Lehenkari","doi":"10.1002/iid3.70312","DOIUrl":"10.1002/iid3.70312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) is known as a cell adhesion receptor which could regulate proliferation and other signaling in cancer. The role of CEACAM6 in pan-gastrointestinal cancers remains largely uncharacterized. This study employed multi-omics bioinformatics to investigate the expression distribution, prognostic value, and immune function of CEACAM6 in these malignancies.
Methods
Utilizing multi-omics data from The Cancer Genome Atlas (TCGA), cBioPortal, GDSC2, TIMER2.0, and TISCH databases, we assessed the CEACAM6 expression and prognostic value across pan-gastrointestinal cancers. Additionally, the potential role of CEACAM6 in the tumor immune microenvironment was explored using multi-omics data, including spatial transcriptomics data.
Results
Based on TCGA data, CEACAM6 was found to be overexpressed in pan-gastrointestinal cancers. The CEACAM6 somatic copy number alterations, DNA methylation and mutation sites were identified as potential contributors to abnormal CEACAM6 expression. The CEACAM6 expression was significantly negatively associated with the abundance of CD4 + Th1 cells across pan-gastrointestinal cancers. Furthermore, spatial transcriptomics data revealed that CEACAM6 expression was significant positively associated with malignant cells, while there was a negative correlation was observed with between CEACAM6 expression and plasma cells.
Conclusion
CEACAM6 exhibits high diagnostic accuracy and tumor-specific overexpression in pan-gastrointestinal cancers. CEACAM6 could promote angiogenesis/metastasis and suppress anti-tumor immunity. Spatially localized in tumors with immune cell exclusion, CEACAM6 correlates with poor survival and immune-excluded subtypes, positioning it as a therapeutic target in precision immunotherapy for pan-gastrointestinal cancers.
{"title":"Integrative Omics Analysis Reveals the Potential Value of CEACAM6 in Pan-Gastrointestinal Cancers","authors":"Liying Jin, Changjuan Tao, Zhiyong Pan, Peng Zhang","doi":"10.1002/iid3.70327","DOIUrl":"10.1002/iid3.70327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) is known as a cell adhesion receptor which could regulate proliferation and other signaling in cancer. The role of CEACAM6 in pan-gastrointestinal cancers remains largely uncharacterized. This study employed multi-omics bioinformatics to investigate the expression distribution, prognostic value, and immune function of CEACAM6 in these malignancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing multi-omics data from The Cancer Genome Atlas (TCGA), cBioPortal, GDSC2, TIMER2.0, and TISCH databases, we assessed the CEACAM6 expression and prognostic value across pan-gastrointestinal cancers. Additionally, the potential role of CEACAM6 in the tumor immune microenvironment was explored using multi-omics data, including spatial transcriptomics data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on TCGA data, CEACAM6 was found to be overexpressed in pan-gastrointestinal cancers. The CEACAM6 somatic copy number alterations, DNA methylation and mutation sites were identified as potential contributors to abnormal CEACAM6 expression. The CEACAM6 expression was significantly negatively associated with the abundance of CD4 + Th1 cells across pan-gastrointestinal cancers. Furthermore, spatial transcriptomics data revealed that CEACAM6 expression was significant positively associated with malignant cells, while there was a negative correlation was observed with between CEACAM6 expression and plasma cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CEACAM6 exhibits high diagnostic accuracy and tumor-specific overexpression in pan-gastrointestinal cancers. CEACAM6 could promote angiogenesis/metastasis and suppress anti-tumor immunity. Spatially localized in tumors with immune cell exclusion, CEACAM6 correlates with poor survival and immune-excluded subtypes, positioning it as a therapeutic target in precision immunotherapy for pan-gastrointestinal cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tumor microcirculation plays a central role in the onset and progression of hypoxia, therapeutic resistance, and immune evasion within the tumor microenvironment. Traditional Chinese Medicine (TCM), characterized by its multi-targeted and systemic regulatory properties, has garnered increasing attention for its potential to modulate this complex milieu.
Methods
We systematically retrieved core literature published between 2003 and 2025 and conducted a comprehensive bibliometric and knowledge-map analysis of 300 representative publications using CiteSpace and VOSviewer. This approach enabled the identification of key modulatory factors, underlying mechanisms, and evolving research trajectories related to TCM-mediated regulation of tumor microcirculation.
Results
Our findings reveal that TCM formulations and their active constituents—such as Tao Hong Si Wu Decoction, ginsenoside Rg3, and tanshinone IIA—modulate angiogenesis and enhance immune cell infiltration through signaling pathways including VEGF, PI3K/AKT, and HIF-1α. Additionally, non-pharmacological interventions such as acupuncture, electroacupuncture, and moxibustion have been shown to normalize vascular structure, modulate glycolytic activity, and reshape immune polarization. Emerging methodologies such as network pharmacology and molecular docking are increasingly utilized to unravel the complex mechanisms of TCM, facilitating the integration of traditional theories with modern scientific frameworks.
Conclusion
TCM exhibits a remarkable capacity for multidimensional regulation of tumor microcirculation. Future efforts should focus on rigorous experimental validation and systems-level modeling to accelerate its clinical translation and incorporation into integrative cancer therapy.
{"title":"Atlas-Based Mapping of Traditional Chinese Medicine Effects on Tumor Microcirculation Regulation","authors":"I Ho, Yijie Xie, Zhipeng Liu, Dingjun Cai","doi":"10.1002/iid3.70347","DOIUrl":"10.1002/iid3.70347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tumor microcirculation plays a central role in the onset and progression of hypoxia, therapeutic resistance, and immune evasion within the tumor microenvironment. Traditional Chinese Medicine (TCM), characterized by its multi-targeted and systemic regulatory properties, has garnered increasing attention for its potential to modulate this complex milieu.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically retrieved core literature published between 2003 and 2025 and conducted a comprehensive bibliometric and knowledge-map analysis of 300 representative publications using CiteSpace and VOSviewer. This approach enabled the identification of key modulatory factors, underlying mechanisms, and evolving research trajectories related to TCM-mediated regulation of tumor microcirculation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings reveal that TCM formulations and their active constituents—such as Tao Hong Si Wu Decoction, ginsenoside Rg3, and tanshinone IIA—modulate angiogenesis and enhance immune cell infiltration through signaling pathways including VEGF, PI3K/AKT, and HIF-1α. Additionally, non-pharmacological interventions such as acupuncture, electroacupuncture, and moxibustion have been shown to normalize vascular structure, modulate glycolytic activity, and reshape immune polarization. Emerging methodologies such as network pharmacology and molecular docking are increasingly utilized to unravel the complex mechanisms of TCM, facilitating the integration of traditional theories with modern scientific frameworks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TCM exhibits a remarkable capacity for multidimensional regulation of tumor microcirculation. Future efforts should focus on rigorous experimental validation and systems-level modeling to accelerate its clinical translation and incorporation into integrative cancer therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bufalin is one main component of the dried venom from Bufo gargarizans Cantor, which has anti-tumor, cardiotonic, anti-inflammatory and other physiological activities. However, in recent years, researchers have mainly paid attention to its anti-tumor effect and neglected its anti-inflammatory effect.
Methods
We used lipopolysaccharide (TLR4 ligand) and poly inosinic acid (TLR3 ligand) to stimulate cultured macrophages to induce inflammatory condition. Transcriptome sequencing and molecular experiments were performed to investigate the underlying mechanism.
Results
Bufalin could significantly reduce the production of pro-inflammatory factors (IL-6, TNF-α, IL-1β, IL-8, CXCL10, etc.), through inhibiting the phosphorylation of IKBα and IRF3, and thus down-regulating Toll-like receptor pathway. Molecular docking predicted that one of the molecular targets of bufalin is MD-2 coupled with lipopolysaccharide-activated TLR4.
Conclusion
These findings not only support the pharmacological basis of using toad to treat inflammatory diseases in the Chinese medical history, but also provide a promising anti-inflammatory drug candidate for future clinical application.
{"title":"Bufalin Inhibits Cytokine Storm by Regulating TLR4/TLR3 Signaling Pathway","authors":"Xixi Liu, Chencheng Li, Jing Yang, Weiguang Zhang, Zhongxiao Hu, Xiaoli Zhang, Reaila Jianati, Fang Tian, Xingbin Dai, Zuqiong Xu, Biqing Chen, Xuejun Zhu","doi":"10.1002/iid3.70318","DOIUrl":"10.1002/iid3.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bufalin is one main component of the dried venom from <i>Bufo gargarizans Cantor</i>, which has anti-tumor, cardiotonic, anti-inflammatory and other physiological activities. However, in recent years, researchers have mainly paid attention to its anti-tumor effect and neglected its anti-inflammatory effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used lipopolysaccharide (TLR4 ligand) and poly inosinic acid (TLR3 ligand) to stimulate cultured macrophages to induce inflammatory condition. Transcriptome sequencing and molecular experiments were performed to investigate the underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bufalin could significantly reduce the production of pro-inflammatory factors (IL-6, TNF-α, IL-1β, IL-8, CXCL10, etc.), through inhibiting the phosphorylation of IKBα and IRF3, and thus down-regulating Toll-like receptor pathway. Molecular docking predicted that one of the molecular targets of bufalin is MD-2 coupled with lipopolysaccharide-activated TLR4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings not only support the pharmacological basis of using toad to treat inflammatory diseases in the Chinese medical history, but also provide a promising anti-inflammatory drug candidate for future clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Objective</h3> <p>Emerging evidence suggests that ferroptosis contributes significantly to the progression of diabetic nephropathy (DN). This study aimed to explore the potential association between dual specificity phosphatase 1 (DUSP1) and ferroptosis in a streptozotocin-induced DN rat model.</p> </section> <section> <h3> Methods</h3> <p>We analyzed microarray datasets (GSE30122 and GSE96804) from the gene expression omnibus (GEO) database to identify ferroptosis-related differentially expressed genes (FDEGs), with particular focus on DUSP1. Experimental validation was performed using 45 specific pathogen-free Sprague-Dawley rats: 15 controls and 30 STZ-induced DN models (60 mg/kg, i.p.). After 12 weeks, successfully modeled rats (<i>n</i> = 28) were randomized into DN (<i>n</i> = 14) and DN+Ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 μmol/kg, <i>n</i> = 14) groups. Renal function parameters (blood urea nitrogen, serum creatinine, urinary albumin) were quantified using automated biochemical analysis. Renal tissue antioxidant capacity (SOD, GSH, MDA) and iron content were assessed. Histopathological evaluation employed HE, Masson, PAS, and Lillie staining. DUSP1 expression was analyzed via immunohistochemistry, Western blot, and RT-qPCR.</p> </section> <section> <h3> Results</h3> <p>DN rats exhibited characteristic metabolic disturbances including polydipsia (394.32 ± 9.92 vs. 28.84 ± 2.45 mL/day, <i>p</i> < 0.001), polyuria, and progressive weight loss. Renal function impairment was evidenced by elevated blood urea nitrogen (2.50 ± 0.46 vs. 11.61 ± 1.61 mmol/L, <i>p</i> < 0.001), serum creatinine (43.01 ± 5.81 vs. 107.62 ± 9.90 μmol/L, <i>p</i> < 0.001), and urine albumin-to-creatinine ratio (18.53 ± 0.92 vs. 269.97 ± 24.59 mg/g, <i>p</i> < 0.001). Fer-1 treatment significantly ameliorated these parameters (<i>p</i> < 0.05) and reduced histopathological damage. DN rats exhibited significantly reduced DUSP1 expression and increased ferroptosis-associated alterations, including elevated ACSL4 expression, enhanced lipid peroxidation, and impaired antioxidant capacity, all of which were partially reversed by Fer-1 treatment (<i>p</i> < 0.001).</p> </section> <section> <h3> Conclusions</h3> <p>Our findings indicate that inhibition of ferroptosis attenuates renal injury in DN and is accompanied by altered DUSP1 expression. These results suggest a potential association between ferroptosis regulation and DUSP1 in DN, providing new insight into ferroptosis-related mechanisms involved in disease progression.</p
目的：越来越多的证据表明，铁下垂在糖尿病肾病（DN）的进展中起着重要作用。本研究旨在探讨双特异性磷酸酶1 （DUSP1）与链脲佐菌素诱导的DN大鼠模型中铁下垂的潜在关联。方法：分析基因表达综合数据库（GEO）中的微阵列数据集（GSE30122和GSE96804），以DUSP1为重点，鉴定与铁衰相关的差异表达基因（FDEGs）。采用45只无特定病原体的Sprague-Dawley大鼠、15只对照组和30只stz诱导DN模型（60 mg/kg, i.p.）进行实验验证。12周后，成功造模的大鼠（n = 28）随机分为DN组（n = 14）和DN+铁抑素-1组（铁抑素-1,2.5 μmol/kg, n = 14）。采用全自动生化分析定量测定肾功能参数（血尿素氮、血清肌酐、尿白蛋白）。测定肾组织抗氧化能力（SOD、GSH、MDA）和铁含量。组织病理学评价采用HE、Masson、PAS和Lillie染色。通过免疫组织化学、Western blot和RT-qPCR分析DUSP1的表达。结果：DN大鼠表现出特征性的代谢紊乱，包括多饮（394.32±9.92 vs 28.84±2.45 mL/d） p。结论：我们的研究结果表明，抑制铁下垂可减轻DN的肾损伤，并伴有DUSP1表达的改变。这些结果表明，在DN中，铁下垂调节与DUSP1之间存在潜在的关联，为参与疾病进展的铁下垂相关机制提供了新的见解。
{"title":"DUSP1 Attenuates Renal Injury in Diabetic Nephropathy by Modulating Ferroptosis: Evidence From Animal Experiments","authors":"Jiarong Liu, Junping Zhang, Yun Zou, Wen Chen, Jixiong Xu","doi":"10.1002/iid3.70340","DOIUrl":"10.1002/iid3.70340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Emerging evidence suggests that ferroptosis contributes significantly to the progression of diabetic nephropathy (DN). This study aimed to explore the potential association between dual specificity phosphatase 1 (DUSP1) and ferroptosis in a streptozotocin-induced DN rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed microarray datasets (GSE30122 and GSE96804) from the gene expression omnibus (GEO) database to identify ferroptosis-related differentially expressed genes (FDEGs), with particular focus on DUSP1. Experimental validation was performed using 45 specific pathogen-free Sprague-Dawley rats: 15 controls and 30 STZ-induced DN models (60 mg/kg, i.p.). After 12 weeks, successfully modeled rats (<i>n</i> = 28) were randomized into DN (<i>n</i> = 14) and DN+Ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 μmol/kg, <i>n</i> = 14) groups. Renal function parameters (blood urea nitrogen, serum creatinine, urinary albumin) were quantified using automated biochemical analysis. Renal tissue antioxidant capacity (SOD, GSH, MDA) and iron content were assessed. Histopathological evaluation employed HE, Masson, PAS, and Lillie staining. DUSP1 expression was analyzed via immunohistochemistry, Western blot, and RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DN rats exhibited characteristic metabolic disturbances including polydipsia (394.32 ± 9.92 vs. 28.84 ± 2.45 mL/day, <i>p</i> < 0.001), polyuria, and progressive weight loss. Renal function impairment was evidenced by elevated blood urea nitrogen (2.50 ± 0.46 vs. 11.61 ± 1.61 mmol/L, <i>p</i> < 0.001), serum creatinine (43.01 ± 5.81 vs. 107.62 ± 9.90 μmol/L, <i>p</i> < 0.001), and urine albumin-to-creatinine ratio (18.53 ± 0.92 vs. 269.97 ± 24.59 mg/g, <i>p</i> < 0.001). Fer-1 treatment significantly ameliorated these parameters (<i>p</i> < 0.05) and reduced histopathological damage. DN rats exhibited significantly reduced DUSP1 expression and increased ferroptosis-associated alterations, including elevated ACSL4 expression, enhanced lipid peroxidation, and impaired antioxidant capacity, all of which were partially reversed by Fer-1 treatment (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that inhibition of ferroptosis attenuates renal injury in DN and is accompanied by altered DUSP1 expression. These results suggest a potential association between ferroptosis regulation and DUSP1 in DN, providing new insight into ferroptosis-related mechanisms involved in disease progression.</p","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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