Pub Date : 2025-10-26DOI: 10.1016/j.cyto.2025.157062
Nicolas J. Wegmann , Dorothea M. Heuberger , Gabor Kadler , Benjamin Seeliger , Thorben Pape , Klaus Stahl , Mattia M. Müller , Sascha David
Introduction
Tie2 is an endothelial surface receptor critically involved in angiogenesis, cell-integrity, and survival. During inflammatory disorders such as sepsis and ARDS, the receptor is shed from the endothelial surface, contributing to a reduction of its protective downstream signaling ultimately contributing to endothelial permeability and thereby capillary leakage. This study investigates the association of the soluble form of Tie2 (sTie2), with multiorgan failure, requirement of dialysis and mortality.
Methodology
We conducted a biomarker study using serum samples from sepsis and/or ARDS patients admitted to the medical intensive care unit (ICU) of Hannover Medical School. sTie2 was quantified by Multiplex Luminex Assay in serum samples collected on the day of ICU admission. Correlations between sTie2 levels and baseline SOFA-score, duration of vasopressor therapy, and duration of mechanical ventilation were evaluated using Pearson's correlation coefficient. The Wilcoxon rank-sum test was employed to compare sTie2 levels between individuals with and without renal replacement therapy, as well as between survivors and non-survivors. Cox regression models were applied to assess the independent association of sTie2 with 28-day mortality.
Results
sTie2 levels showed an inverse correlation with the SOFA-score (R = −0.2, p = 0.003) and were lower in patients requiring renal replacement therapy (17.4 [12.25–22.48] vs. 21.35 [14.91–29.08] ng/ml, p = 0.003) and in non-survivors (14.54 [10.96–15.02] vs. 21.01 [15–28.12] ng/ml, p < 0.001). No correlation was found between sTie2 and the number of days requiring vasopressor therapy or mechanical ventilation. Using multivariable cox regression, sTie2 was independently associated with mortality at 28-days (sTie2, log(ng/ml) – HR 0.35, 95% CI 0.21–0.57, p < 0.001).
Conclusion
In this study of severely ill ICU patients, sTie2 was inversely related to severity of disease and to outcome. If the decrease in sTie2 is adaptive or maladaptive remains unclear but future investigations are required analysing the exact pathophysiological role of sTie2 to evaluate the biomarker as a potential target for the treatment of capillary leakage in patients with sepsis and/or ARDS.
{"title":"Association of the soluble form of the endothelial Tie2 receptor with organ failure and mortality in patients with sepsis and ARDS","authors":"Nicolas J. Wegmann , Dorothea M. Heuberger , Gabor Kadler , Benjamin Seeliger , Thorben Pape , Klaus Stahl , Mattia M. Müller , Sascha David","doi":"10.1016/j.cyto.2025.157062","DOIUrl":"10.1016/j.cyto.2025.157062","url":null,"abstract":"<div><h3>Introduction</h3><div>Tie2 is an endothelial surface receptor critically involved in angiogenesis, cell-integrity, and survival. During inflammatory disorders such as sepsis and ARDS, the receptor is shed from the endothelial surface, contributing to a reduction of its protective downstream signaling ultimately contributing to endothelial permeability and thereby capillary leakage. This study investigates the association of the soluble form of Tie2 (sTie2), with multiorgan failure, requirement of dialysis and mortality.</div></div><div><h3>Methodology</h3><div>We conducted a biomarker study using serum samples from sepsis and/or ARDS patients admitted to the medical intensive care unit (ICU) of Hannover Medical School. sTie2 was quantified by Multiplex Luminex Assay in serum samples collected on the day of ICU admission. Correlations between sTie2 levels and baseline SOFA-score, duration of vasopressor therapy, and duration of mechanical ventilation were evaluated using Pearson's correlation coefficient. The Wilcoxon rank-sum test was employed to compare sTie2 levels between individuals with and without renal replacement therapy, as well as between survivors and non-survivors. Cox regression models were applied to assess the independent association of sTie2 with 28-day mortality.</div></div><div><h3>Results</h3><div>sTie2 levels showed an inverse correlation with the SOFA-score (<em>R</em> = −0.2, <em>p</em> = 0.003) and were lower in patients requiring renal replacement therapy (17.4 [12.25–22.48] vs. 21.35 [14.91–29.08] ng/ml, p = 0.003) and in non-survivors (14.54 [10.96–15.02] vs. 21.01 [15–28.12] ng/ml, <em>p</em> < 0.001). No correlation was found between sTie2 and the number of days requiring vasopressor therapy or mechanical ventilation. Using multivariable cox regression, sTie2 was independently associated with mortality at 28-days (sTie2, log(ng/ml) – HR 0.35, 95% CI 0.21–0.57, <em>p</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>In this study of severely ill ICU patients, sTie2 was inversely related to severity of disease and to outcome. If the decrease in sTie2 is adaptive or maladaptive remains unclear but future investigations are required analysing the exact pathophysiological role of sTie2 to evaluate the biomarker as a potential target for the treatment of capillary leakage in patients with sepsis and/or ARDS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157062"},"PeriodicalIF":3.7,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1016/j.cyto.2025.157043
Emmerson C.F. de Farias , Patricia B. Carvalho , Luciana M.P.P. do Nascimento , Andreza H.O. Pinheiro , Marília C.B. Alves , Kíssila M.M. Machado-Ferraro , Larisse F.Q. Aires , Luana G. Dias , Mayara M.M. Machado , Michaelle J.D. Serrão , Raphaella R. Gomes , Sara M.P. de Moraes , Gabriela C.L. Pontes , Railana D.F.P. Carvalho , Elaine B.G.P. Nascimento , Cristiane T.C. Silva , Adriana M.B. de Sousa , Lêda L. da Silva , Nathália K.F. Barbosa , Anna L.M. Machado , Marta C. Monteiro
Background
Multiple organ dysfunction syndrome (MODS) remains a major cause of morbidity and mortality in pediatric intensive care units (PICUs), particularly when triggered by SARS-CoV-2 or bacterial sepsis. This study aimed to investigate the association between inflammatory and oxidative stress biomarkers and the development and outcome of MODS in critically ill children with confirmed SARS-CoV-2 or bacterial infections.
Methods
In this prospective, single-center cohort study (May 2020–December 2024), 62 pediatric patients (29 days to <18 years) were stratified into three groups: SARS-CoV-2 without MODS (n = 22), SARS-CoV-2 with MODS (n = 20), and bacterial MODS (n = 20). Circulating cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A) and oxidative stress markers (GSH, TBARS, TEAC) were quantified at PICU admission and on day 5. Associations with organ dysfunction and 28-day mortality were assessed using non-parametric statistical analyses and Kaplan-Meier survival estimates.
Results
MODS groups exhibited on day 1 sustained elevations in TNF-α, IFN-γ, and IL-17A—most pronounced in bacterial MODS (Group 3; p < 0.0001). IFN-γ was notably increased in viral MODS (Group 2). Group 3 also showed marked elevations in IL-6, IL-2, and IL-10 (p < 0.0001). By day 5, both MODS groups demonstrated significant reduced GSH and TEAC and elevated TBARS, the most severe in Group 3. In contrast, Group 1 exhibited stable cytokine profiles and preserved antioxidant status throughout. Non-survivors showed persistently elevated IL-6, TNF-α, IFN-γ, and IL-17A, coupled with sustained depletion of GSH and TEAC, and increased TBARS levels (all p < 0.0001). IL-6 and IFN-γ were particularly elevated in non-survivors with bacterial and viral MODS, respectively. Biomarker trajectories diverged between survivors and non-survivors by day 5, with failure to normalize immune-redox profiles associated with mortality. Accessible indices such as NLR, CAR, and VIS correlated with biomarker levels and disease severity. Kaplan–Meier analysis confirmed reduced survival in MODS groups (p = 0.0005).
Conclusions
A distinct cytokine and oxidative stress signature—marked by early and sustained elevations in IL-6, TNF-α, IFN-γ, IL-17A, and TBARS, and depletion of GSH and TEAC—is associated with mortality in pediatric MODS. Bacterial MODS was distinguished by the most severe immune-redox imbalance. Integrated immune-redox profiling offers prognostic value and may inform precision-targeted interventions, particularly in resource-limited settings.
{"title":"IL-6, IFN-γ, IL-17A elevations and glutathione depletion predict severe MODS and mortality in critically ill children with COVID-19 and bacterial sepsis: a prospective cohort study from the Brazilian Amazon","authors":"Emmerson C.F. de Farias , Patricia B. Carvalho , Luciana M.P.P. do Nascimento , Andreza H.O. Pinheiro , Marília C.B. Alves , Kíssila M.M. Machado-Ferraro , Larisse F.Q. Aires , Luana G. Dias , Mayara M.M. Machado , Michaelle J.D. Serrão , Raphaella R. Gomes , Sara M.P. de Moraes , Gabriela C.L. Pontes , Railana D.F.P. Carvalho , Elaine B.G.P. Nascimento , Cristiane T.C. Silva , Adriana M.B. de Sousa , Lêda L. da Silva , Nathália K.F. Barbosa , Anna L.M. Machado , Marta C. Monteiro","doi":"10.1016/j.cyto.2025.157043","DOIUrl":"10.1016/j.cyto.2025.157043","url":null,"abstract":"<div><h3>Background</h3><div>Multiple organ dysfunction syndrome (MODS) remains a major cause of morbidity and mortality in pediatric intensive care units (PICUs), particularly when triggered by SARS-CoV-2 or bacterial sepsis. This study aimed to investigate the association between inflammatory and oxidative stress biomarkers and the development and outcome of MODS in critically ill children with confirmed SARS-CoV-2 or bacterial infections.</div></div><div><h3>Methods</h3><div>In this prospective, single-center cohort study (May 2020–December 2024), 62 pediatric patients (29 days to <18 years) were stratified into three groups: SARS-CoV-2 without MODS (<em>n</em> = 22), SARS-CoV-2 with MODS (<em>n</em> = 20), and bacterial MODS (n = 20). Circulating cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A) and oxidative stress markers (GSH, TBARS, TEAC) were quantified at PICU admission and on day 5. Associations with organ dysfunction and 28-day mortality were assessed using non-parametric statistical analyses and Kaplan-Meier survival estimates.</div></div><div><h3>Results</h3><div>MODS groups exhibited on day 1 sustained elevations in TNF-α, IFN-γ, and IL-17A—most pronounced in bacterial MODS (Group 3; <em>p</em> < 0.0001). IFN-γ was notably increased in viral MODS (Group 2). Group 3 also showed marked elevations in IL-6, IL-2, and IL-10 (p < 0.0001). By day 5, both MODS groups demonstrated significant reduced GSH and TEAC and elevated TBARS, the most severe in Group 3. In contrast, Group 1 exhibited stable cytokine profiles and preserved antioxidant status throughout. Non-survivors showed persistently elevated IL-6, TNF-α, IFN-γ, and IL-17A, coupled with sustained depletion of GSH and TEAC, and increased TBARS levels (all <em>p</em> < 0.0001). IL-6 and IFN-γ were particularly elevated in non-survivors with bacterial and viral MODS, respectively. Biomarker trajectories diverged between survivors and non-survivors by day 5, with failure to normalize immune-redox profiles associated with mortality. Accessible indices such as NLR, CAR, and VIS correlated with biomarker levels and disease severity. Kaplan–Meier analysis confirmed reduced survival in MODS groups (<em>p</em> = 0.0005).</div></div><div><h3>Conclusions</h3><div>A distinct cytokine and oxidative stress signature—marked by early and sustained elevations in IL-6, TNF-α, IFN-γ, IL-17A, and TBARS, and depletion of GSH and TEAC—is associated with mortality in pediatric MODS. Bacterial MODS was distinguished by the most severe immune-redox imbalance. Integrated immune-redox profiling offers prognostic value and may inform precision-targeted interventions, particularly in resource-limited settings.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157043"},"PeriodicalIF":3.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1016/j.cyto.2025.157052
Chang Liu, Yi Wei, Fengchuan Jing , Qijian Yi
Background
Kawasaki disease (KD), an acute vasculitis of unclear etiology, is an important contributor to childhood-acquired heart disease due to coronary arterial aneurysms (CAAs). Current diagnosis lacks specific biomarkers, risking delayed treatment. Endocan, a proteoglycan implicated in vascular inflammation, may address this gap. This study evaluates serum endocan in acute KD for its utility in early KD diagnosis and CAA risk prediction.
Method
This prospective cohort study enrolled 79 KD patients and 48 healthy controls. The KD group was further divided into KD with CAA (KD-CAA) and KD non-CAA (KD-NCAA) subgroups. Serum endocan levels were quantified via enzyme-linked immunosorbent assay. Clinical parameters including inflammatory markers were systematically analyzed using SPSS and GraphPad Prism.
Results
Serum endocan levels were significantly elevated in KD patients compared to HCs (median [25th–75th percentile], 1803.69 pg/ml [1478.97–2038.87] vs. 931.73 [815.57–1138.72] pg/ml, P < 0.001), with higher concentrations in KD-CAA versus KD-NCAA (mean ± SD, 1962.43 ± 321.48 vs. 1702.46 ± 458.54 pg/ml, P = 0.024).
Endocan demonstrated excellent performance in distinguishing KD patients from HCs (AUC = 0.915, 95 % CI: 0.863–0.968; sensitivity 88.6 %, specificity 85.4 %). It also showed a modest but statistically significant predictive value for CAAs within the KD cohort (AUC = 0.675, 95 % CI: 0.548–0.801; sensitivity 73.7 %, specificity 58.3 %).
Conclusion
Serum endocan is a high-performance biomarker for differentiating KD from HCs. Despite modest performance in predicting CAAs and undetermined specificity, it may serve as a valuable supportive tool for risk stratification in KD patients.
{"title":"Serum endocan as a dual-function biomarker in Kawasaki disease: early diagnostic potential and prediction of coronary arterial aneurysms","authors":"Chang Liu, Yi Wei, Fengchuan Jing , Qijian Yi","doi":"10.1016/j.cyto.2025.157052","DOIUrl":"10.1016/j.cyto.2025.157052","url":null,"abstract":"<div><h3>Background</h3><div>Kawasaki disease (KD), an acute vasculitis of unclear etiology, is an important contributor to childhood-acquired heart disease due to coronary arterial aneurysms (CAAs). Current diagnosis lacks specific biomarkers, risking delayed treatment. Endocan, a proteoglycan implicated in vascular inflammation, may address this gap. This study evaluates serum endocan in acute KD for its utility in early KD diagnosis and CAA risk prediction.</div></div><div><h3>Method</h3><div>This prospective cohort study enrolled 79 KD patients and 48 healthy controls. The KD group was further divided into KD with CAA (KD-CAA) and KD non-CAA (KD-NCAA) subgroups. Serum endocan levels were quantified via enzyme-linked immunosorbent assay. Clinical parameters including inflammatory markers were systematically analyzed using SPSS and GraphPad Prism.</div></div><div><h3>Results</h3><div>Serum endocan levels were significantly elevated in KD patients compared to HCs (median [25th–75th percentile], 1803.69 pg/ml [1478.97–2038.87] vs. 931.73 [815.57–1138.72] pg/ml, <em>P</em> < 0.001), with higher concentrations in KD-CAA versus KD-NCAA (mean ± SD, 1962.43 ± 321.48 vs. 1702.46 ± 458.54 pg/ml, <em>P</em> = 0.024).</div><div>Endocan demonstrated excellent performance in distinguishing KD patients from HCs (AUC = 0.915, 95 % CI: 0.863–0.968; sensitivity 88.6 %, specificity 85.4 %). It also showed a modest but statistically significant predictive value for CAAs within the KD cohort (AUC = 0.675, 95 % CI: 0.548–0.801; sensitivity 73.7 %, specificity 58.3 %).</div></div><div><h3>Conclusion</h3><div>Serum endocan is a high-performance biomarker for differentiating KD from HCs. Despite modest performance in predicting CAAs and undetermined specificity, it may serve as a valuable supportive tool for risk stratification in KD patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157052"},"PeriodicalIF":3.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1016/j.cyto.2025.157061
Jianna Mao, Yuhou Shen, Hongyang Qi
Background
Helicobacter pylori infection is a major risk factor for the development of peptic ulcer disease and associated cancers, posing a significant public health concern. Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in mucosal healing and may modulate H. pylori–induced gastric injury. In this study, we investigated the role of PPARγ in the progression of H. pylori–induced gastric ulceration.
Method
The potential association between PPARγ level and H. pylori infection rate was firstly analyzed with clinical samples. Then the effects of PPARγ activation on H. pylori–induced inflammation in human gastric epithelial cells (HGECs) were evaluated using CCK-8 assays for cell viability and immunofluorescence for inflammatory markers. The expression of PPARγ downstream effectors, including TLRs/NF-κB axis was also detected.
Results
Clinical analysis revealed that H. pylori infection significantly increased the risk of gastric ulcer development. PPARγ levels were inversely correlated with H. pylori infection rate and with the concentrations of IL-6, IL-1β, and TNF-α. In HGECs, lipopolysaccharide (LPS) treatment induced abnormal cell viability and heightened inflammatory responses, both of which were attenuated by the PPARγ agonist pioglitazone. Pioglitazone selectively promoted apoptosis in LPS-treated cells. At the molecular level, LPS increased expression of TLR2, TLR4, and TLR5, leading to NF-κB pathway activation; PPARγ activation suppressed both TLR expression and NF-κB signaling, coinciding with reduced cytokine release.
Conclusions
The current study demonstrates that PPARγ activation exerts anti–H. pylori effects during gastric ulcer progression by inhibiting the TLR/NF-κB signaling pathway.
{"title":"Inflammation in gastric epithelium associated with infection of Helicobacter pylori is induced by inhibited PPARγ pathway: the key role of TLRs/NF-κB axis","authors":"Jianna Mao, Yuhou Shen, Hongyang Qi","doi":"10.1016/j.cyto.2025.157061","DOIUrl":"10.1016/j.cyto.2025.157061","url":null,"abstract":"<div><h3>Background</h3><div><em>Helicobacter pylori</em> infection is a major risk factor for the development of peptic ulcer disease and associated cancers, posing a significant public health concern. Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in mucosal healing and may modulate <em>H. pylori</em>–induced gastric injury. In this study, we investigated the role of PPARγ in the progression of <em>H. pylori</em>–induced gastric ulceration.</div></div><div><h3>Method</h3><div>The potential association between PPARγ level and <em>H. pylori</em> infection rate was firstly analyzed with clinical samples. Then the effects of PPARγ activation on <em>H. pylori</em>–induced inflammation in human gastric epithelial cells (HGECs) were evaluated using CCK-8 assays for cell viability and immunofluorescence for inflammatory markers. The expression of PPARγ downstream effectors, including TLRs/NF-κB axis was also detected.</div></div><div><h3>Results</h3><div>Clinical analysis revealed that <em>H. pylori</em> infection significantly increased the risk of gastric ulcer development. PPARγ levels were inversely correlated with <em>H. pylori</em> infection rate and with the concentrations of IL-6, IL-1β, and TNF-α. In HGECs, lipopolysaccharide (LPS) treatment induced abnormal cell viability and heightened inflammatory responses, both of which were attenuated by the PPARγ agonist pioglitazone. Pioglitazone selectively promoted apoptosis in LPS-treated cells. At the molecular level, LPS increased expression of TLR2, TLR4, and TLR5, leading to NF-κB pathway activation; PPARγ activation suppressed both TLR expression and NF-κB signaling, coinciding with reduced cytokine release.</div></div><div><h3>Conclusions</h3><div>The current study demonstrates that PPARγ activation exerts anti–<em>H. pylori</em> effects during gastric ulcer progression by inhibiting the TLR/NF-κB signaling pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157061"},"PeriodicalIF":3.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.cyto.2025.157058
Zhi Li , Wen Qin , Xiudi Wu , Mingcai Li , Yan Li
Background: Polymyositis (PM) and dermatomyositis (DM) are two common subtypes of idiopathic inflammatory myopathies (IIM). The concentration of serum interleukin (IL)-41 in patients with PM/DM has not been reported. This study aims to investigate the levels of IL-41 in the serum of individuals diagnosed with PM/DM.
Methods: A total of 118 participants were enrolled in the study, comprising 80 patients with PM/DM and 38 healthy controls (HC). Comprehensive clinical data for each participant were collected through physical examinations and detailed clinical histories. The levels of IL-41 were quantified using the enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was employed to examine the relationship between IL-41 levels and various clinical parameters. The diagnostic potential of IL-41 was assessed using the receiver operating characteristic (ROC) curve.
Results: Serum IL-41 levels were significantly elevated in PM/DM patients with interstitial lung disease (ILD) compared to HC [1001.03 (572.95, 1604.83) pg/mL vs 361.03 (302.24, 541.06) pg/mL, P < 0.0001]. Furthermore, a significant difference was also observed in serum IL-41 levels between PM/DM patients without ILD and HC [561.81 (407.94, 827.34) pg/mL vs 361.03 (302.24, 541.06) pg/mL, P = 0.0139]. IL-41 exhibits substantial diagnostic potential for PM/DM, and its combination with lactate dehydrogenase enhances diagnostic efficacy. Moreover, IL-41 acts as an independent risk factor for the onset of PM/DM.
Conclusions: This study revealed that serum IL-41 levels are elevated in patients with PM/DM, suggesting that IL-41 could serve as a novel biomarker for the identification of these conditions.
{"title":"Unveiling IL-41: A novel biomarker for polymyositis and dermatomyositis diagnosis","authors":"Zhi Li , Wen Qin , Xiudi Wu , Mingcai Li , Yan Li","doi":"10.1016/j.cyto.2025.157058","DOIUrl":"10.1016/j.cyto.2025.157058","url":null,"abstract":"<div><div><em>Background:</em> Polymyositis (PM) and dermatomyositis (DM) are two common subtypes of idiopathic inflammatory myopathies (IIM). The concentration of serum interleukin (IL)-41 in patients with PM/DM has not been reported. This study aims to investigate the levels of IL-41 in the serum of individuals diagnosed with PM/DM.</div><div><em>Methods:</em> A total of 118 participants were enrolled in the study, comprising 80 patients with PM/DM and 38 healthy controls (HC). Comprehensive clinical data for each participant were collected through physical examinations and detailed clinical histories. The levels of IL-41 were quantified using the enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was employed to examine the relationship between IL-41 levels and various clinical parameters. The diagnostic potential of IL-41 was assessed using the receiver operating characteristic (ROC) curve.</div><div><em>Results:</em> Serum IL-41 levels were significantly elevated in PM/DM patients with interstitial lung disease (ILD) compared to HC [1001.03 (572.95, 1604.83) pg/mL vs 361.03 (302.24, 541.06) pg/mL, <em>P</em> < 0.0001]. Furthermore, a significant difference was also observed in serum IL-41 levels between PM/DM patients without ILD and HC [561.81 (407.94, 827.34) pg/mL vs 361.03 (302.24, 541.06) pg/mL, <em>P</em> = 0.0139]. IL-41 exhibits substantial diagnostic potential for PM/DM, and its combination with lactate dehydrogenase enhances diagnostic efficacy. Moreover, IL-41 acts as an independent risk factor for the onset of PM/DM.</div><div><em>Conclusions:</em> This study revealed that serum IL-41 levels are elevated in patients with PM/DM, suggesting that IL-41 could serve as a novel biomarker for the identification of these conditions.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157058"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To examine whether serum interleukin-1β (IL-1β) or IL-1 receptor antagonist (IL-1Ra) levels are associated with disease activity or relapse risk in large vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK).
Methods
Twenty one patients with treatment-naive, active LVV (13 with GCA and 8 with TAK), and 14 healthy individuals were enrolled in the study. Serum levels of IL-1β, IL-1Ra, IL-2, IL-6, IL-12p40, IL-17, IL-23, IFN-γ, and TNF-α were measured. Association with C-reactive protein (CRP) levels, Indian Takayasu clinical activity score (ITAS-A), and relapse were analyzed.
Results
IL-1Ra levels were significantly higher in patients with with TAK (465.3 pg/mL) and GCA (384.9 pg/mL) compared to healthy individuals (170.4 pg/mL; p < 0.001). IL-6 levels were also elevated in LVV, while IL-1β and IFN-γ were increased only in GCA and IL-17 levels were increased only in TAK. IL-1Ra levels positively correlated with ITAS-A scores in TAK and with CRP levels in GCA. IL-6 correlated with CRP in both diseases; IL-1β and other cytokines showed no such association. During follow-up, six patients (five with GCA and one with TAK) experienced symptomatic relapse. In GCA, baseline IL-1Ra levels were significantly lower in those who relapsed compared to non-relapsed patients (270.8 vs. 616.4 pg/mL; p = 0.008). No significant difference in other cytokine levels were observed. Receiver operating characteristic analysis demonstrated that IL-1Ra levels >340.4 pg/mL could distinguish non-relapsed from relapsed cases (AUC = 0.95).
Conclusion
Serum IL-1Ra levels correlate with CRP levels in GCA and ITAS-A scores in TAK and serve as a predictive biomarker for relapse.
{"title":"Serum interleukin-1 receptor antagonist levels are a useful marker of disease activity and risk of relapse in large vessel vasculitis.","authors":"Koji Suzuki , Sho Ishigaki , Mitsuhiro Akiyama , Keiko Yoshimoto , Waleed Alshehri , Kanako Shimanuki , Koichi Saito , Hiroshi Takei , Noriyasu Seki , Hideto Tsujimoto , Kenji Chiba , Yuko Kaneko","doi":"10.1016/j.cyto.2025.157059","DOIUrl":"10.1016/j.cyto.2025.157059","url":null,"abstract":"<div><h3>Objective</h3><div>To examine whether serum interleukin-1β (IL-1β) or IL-1 receptor antagonist (IL-1Ra) levels are associated with disease activity or relapse risk in large vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK).</div></div><div><h3>Methods</h3><div>Twenty one patients with treatment-naive, active LVV (13 with GCA and 8 with TAK), and 14 healthy individuals were enrolled in the study. Serum levels of IL-1β, IL-1Ra, IL-2, IL-6, IL-12p40, IL-17, IL-23, IFN-γ, and TNF-α were measured. Association with C-reactive protein (CRP) levels, Indian Takayasu clinical activity score (ITAS-A), and relapse were analyzed.</div></div><div><h3>Results</h3><div>IL-1Ra levels were significantly higher in patients with with TAK (465.3 pg/mL) and GCA (384.9 pg/mL) compared to healthy individuals (170.4 pg/mL; <em>p</em> < 0.001). IL-6 levels were also elevated in LVV, while IL-1β and IFN-γ were increased only in GCA and IL-17 levels were increased only in TAK. IL-1Ra levels positively correlated with ITAS-A scores in TAK and with CRP levels in GCA. IL-6 correlated with CRP in both diseases; IL-1β and other cytokines showed no such association. During follow-up, six patients (five with GCA and one with TAK) experienced symptomatic relapse. In GCA, baseline IL-1Ra levels were significantly lower in those who relapsed compared to non-relapsed patients (270.8 vs. 616.4 pg/mL; <em>p</em> = 0.008). No significant difference in other cytokine levels were observed. Receiver operating characteristic analysis demonstrated that IL-1Ra levels >340.4 pg/mL could distinguish non-relapsed from relapsed cases (AUC = 0.95).</div></div><div><h3>Conclusion</h3><div>Serum IL-1Ra levels correlate with CRP levels in GCA and ITAS-A scores in TAK and serve as a predictive biomarker for relapse.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157059"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.cyto.2025.157057
Huriye Ezveci , Sukran Dogru , Fikriye Karanfil Yaman , Pelin Bahçeci , Hatice Bedia Yildiz , Meltem Uyaner Kan , İbrahim Kilinç , Kazım Gezginç
Objective
The study aims to evaluate the prediction of gestational diabetes mellitus (GDM) by proinflammatory resistin, chemerin, and progranulin, as well as anti-inflammatory adipokines omentin and IL-10, in maternal serum during the first trimester.
Material method
This prospective case-control study was performed in the obstetric unit of the university hospital from January 2023 to July 2024. Maternal serum samples from the study cases were collected during the first-trimester screening test to analyze resistin, chemerin, progranulin, omentin, and IL-10 levels. The cases were subsequently categorized into groups diagnosed with GDM and those not diagnosed between 24 and 28 weeks. Clinical and laboratory assessments were conducted.
Results
The study included a total of 160 pregnant women. 38 of these patients had GDM, and 122 had control cases. In the serum samples taken in the first trimester, resistin, chemerin, and IL-10 levels did not create a statistically significant difference in the GDM and control groups (p > 0.05). Statistical differences were observed between the groups in progranulin and omentin levels (p = 0.042, p = 0.004, respectively). For predicting GDM, the optimum cut-off value was 83.5 for progranulin (sensitivity: 57.9 %, specificity: 63.9 %, PPV: 33.3 %, NPV: 83 %) and 2.5 for omentin (sensitivity: 73.7 %, specificity: 58.2 %, PPV: 35.4 %, NPV: 87.7 %).
Conclusion
First-trimester progranulin and omentin levels may be useful in excluding GDM, but they lack sufficient power to diagnose it.
{"title":"First-trimester prediction of gestational diabetes mellitus using resistin, chemerin, progranulin, omentin, and IL-10","authors":"Huriye Ezveci , Sukran Dogru , Fikriye Karanfil Yaman , Pelin Bahçeci , Hatice Bedia Yildiz , Meltem Uyaner Kan , İbrahim Kilinç , Kazım Gezginç","doi":"10.1016/j.cyto.2025.157057","DOIUrl":"10.1016/j.cyto.2025.157057","url":null,"abstract":"<div><h3>Objective</h3><div>The study aims to evaluate the prediction of gestational diabetes mellitus (GDM) by proinflammatory resistin, chemerin, and progranulin, as well as anti-inflammatory adipokines omentin and IL-10, in maternal serum during the first trimester.</div></div><div><h3>Material method</h3><div>This prospective case-control study was performed in the obstetric unit of the university hospital from January 2023 to July 2024. Maternal serum samples from the study cases were collected during the first-trimester screening test to analyze resistin, chemerin, progranulin, omentin, and IL-10 levels. The cases were subsequently categorized into groups diagnosed with GDM and those not diagnosed between 24 and 28 weeks. Clinical and laboratory assessments were conducted.</div></div><div><h3>Results</h3><div>The study included a total of 160 pregnant women. 38 of these patients had GDM, and 122 had control cases. In the serum samples taken in the first trimester, resistin, chemerin, and IL-10 levels did not create a statistically significant difference in the GDM and control groups (<em>p</em> > 0.05). Statistical differences were observed between the groups in progranulin and omentin levels (<em>p</em> = 0.042, <em>p</em> = 0.004, respectively). For predicting GDM, the optimum cut-off value was 83.5 for progranulin (sensitivity: 57.9 %, specificity: 63.9 %, PPV: 33.3 %, NPV: 83 %) and 2.5 for omentin (sensitivity: 73.7 %, specificity: 58.2 %, PPV: 35.4 %, NPV: 87.7 %).</div></div><div><h3>Conclusion</h3><div>First-trimester progranulin and omentin levels may be useful in excluding GDM, but they lack sufficient power to diagnose it.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157057"},"PeriodicalIF":3.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-15DOI: 10.1016/j.cyto.2025.157053
Takao Kobayashi , Sota Iwatani , Toshihiko Ikuta, Seiji Yoshimoto
Background
Peri-operative management in congenital diaphragmatic hernia (CDH) remains a significant challenge associated with mortality and morbidity. Although interleukin-6 (IL-6) reflects surgical stress in adults, its peri-operative dynamics in newborns remain unclear. This study investigated changes in IL-6 levels in CDH newborns and their association with surgical stress factors and post-operative complications.
Methods
In this single-center study, CDH newborns who underwent surgical repair between 2010 and 2022 were retrospectively studied. Changes in serum IL-6 and C-reactive protein (CRP) levels from 72-h pre-operatively to 96-h post-operatively were assessed. Correlations between peak peri-operative IL-6/CRP levels and surgical stress-related factors or early post-operative complications were also explored in this preliminary analysis.
Results
Of 49 newborns, 20 had available data to evaluate peri-operative IL-6 and CRP levels. Serum IL-6 peaked [median: 122.7 (62–1898) pg/mL] at 10-h (1–42) postoperatively, while CRP peaked [median: 2.40 (0.24–8.31) mg/dL] at 38-h (12–47). Peak IL-6 levels correlated negatively with postnatal time (rs = −0.610) and positively with intra-operative blood loss and 24-h post-operative transfusion volumes (rs = 0.497 and 0.510).
Conclusions
In CDH newborns, serum IL-6 levels increase during the 24–48-h post-operative period and return to baseline by the 48–72-h period. Although this is a preliminary study with a limited sample size, assessing peak IL-6 levels may provide a useful indicator of surgical stress and help optimize peri-operative management, including transfusion strategies.
{"title":"Serum IL-6 levels correlate with surgical stress factors in newborns with congenital diaphragmatic hernia","authors":"Takao Kobayashi , Sota Iwatani , Toshihiko Ikuta, Seiji Yoshimoto","doi":"10.1016/j.cyto.2025.157053","DOIUrl":"10.1016/j.cyto.2025.157053","url":null,"abstract":"<div><h3>Background</h3><div>Peri-operative management in congenital diaphragmatic hernia (CDH) remains a significant challenge associated with mortality and morbidity. Although interleukin-6 (IL-6) reflects surgical stress in adults, its peri-operative dynamics in newborns remain unclear. This study investigated changes in IL-6 levels in CDH newborns and their association with surgical stress factors and post-operative complications.</div></div><div><h3>Methods</h3><div>In this single-center study, CDH newborns who underwent surgical repair between 2010 and 2022 were retrospectively studied. Changes in serum IL-6 and C-reactive protein (CRP) levels from 72-h pre-operatively to 96-h post-operatively were assessed. Correlations between peak peri-operative IL-6/CRP levels and surgical stress-related factors or early post-operative complications were also explored in this preliminary analysis.</div></div><div><h3>Results</h3><div>Of 49 newborns, 20 had available data to evaluate peri-operative IL-6 and CRP levels. Serum IL-6 peaked [median: 122.7 (62–1898) pg/mL] at 10-h (1–42) postoperatively, while CRP peaked [median: 2.40 (0.24–8.31) mg/dL] at 38-h (12–47). Peak IL-6 levels correlated negatively with postnatal time (<em>r</em><sub><em>s</em></sub> = −0.610) and positively with intra-operative blood loss and 24-h post-operative transfusion volumes (<em>r</em><sub><em>s</em></sub> = 0.497 and 0.510).</div></div><div><h3>Conclusions</h3><div>In CDH newborns, serum IL-6 levels increase during the 24–48-h post-operative period and return to baseline by the 48–72-h period. Although this is a preliminary study with a limited sample size, assessing peak IL-6 levels may provide a useful indicator of surgical stress and help optimize peri-operative management, including transfusion strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157053"},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/j.cyto.2025.157055
Fatih Serdar Baykal , Serdar Can Güven , Ahmet Kor , Funda Eren , Salim Neşelioğlu , Bünyamin Polat , Serdar Esmer , Berkan Armağan , Kevser Orhan , İsmail Doğan , Yüksel Maraş , Salih Başer , Özcan Erel , Şükran Erten
Aim of this study was to evaluate plasma netrin-1 levels in axial spondyloarthritis and to investigate relations between disease activity and other parameters. Axial spondyloarthritis is a term defining a form of the spondyloarthritis in which axial skeleton is predominantly affected. Netrin-1 is a laminin-like matrix protein belonging to the axonal guide protein family, controlling neuronal migration in the embryonic period and inhibiting leukocyte aggregation to provide neuronal protection in the tissue. Study was conducted cross-sectional. Patients with axial spondyloarthritis between ages of 18–65 who applied to our outpatient clinic were enrolled upon consent. A control group was formed by healthy volunteers. Demographics, clinic, laboratory, imaging data and disease activity scores were recorded. Spondyloarthritis patients were subgrouped as ankylosing spondylitis and non-radiographic axial spondyloarthritis. Serum netrin-1 was measured by a commercial kit in patient and control groups. A total of 60 spondyloarthritis patients and 56 healthy controls were enrolled. No significant differences in serum netrin-1 levels were observed among patient groups and controls. Netrin-1 levels had a significant positive correlation with disease activity parameters and found to be higher in patients with higher disease activity. Receiver operating curve analyses revealed fair discriminative power for active disease. Our results suggest a utility for netrin-1 as a novel biomarker for detecting disease activity in spondyloarthritis, for the first time to the best of our knowledge.
{"title":"The relationship of plasma netrin-1 level with disease activity and other parameters in patients with axial spondyloarthritis","authors":"Fatih Serdar Baykal , Serdar Can Güven , Ahmet Kor , Funda Eren , Salim Neşelioğlu , Bünyamin Polat , Serdar Esmer , Berkan Armağan , Kevser Orhan , İsmail Doğan , Yüksel Maraş , Salih Başer , Özcan Erel , Şükran Erten","doi":"10.1016/j.cyto.2025.157055","DOIUrl":"10.1016/j.cyto.2025.157055","url":null,"abstract":"<div><div>Aim of this study was to evaluate plasma netrin-1 levels in axial spondyloarthritis and to investigate relations between disease activity and other parameters. Axial spondyloarthritis is a term defining a form of the spondyloarthritis in which axial skeleton is predominantly affected. Netrin-1 is a laminin-like matrix protein belonging to the axonal guide protein family, controlling neuronal migration in the embryonic period and inhibiting leukocyte aggregation to provide neuronal protection in the tissue. Study was conducted cross-sectional<strong>.</strong> Patients with axial spondyloarthritis between ages of 18–65 who applied to our outpatient clinic were enrolled upon consent. A control group was formed by healthy volunteers. Demographics, clinic, laboratory, imaging data and disease activity scores were recorded. Spondyloarthritis patients were subgrouped as ankylosing spondylitis and non-radiographic axial spondyloarthritis. Serum netrin-1 was measured by a commercial kit in patient and control groups. A total of 60 spondyloarthritis patients and 56 healthy controls were enrolled. No significant differences in serum netrin-1 levels were observed among patient groups and controls. Netrin-1 levels had a significant positive correlation with disease activity parameters and found to be higher in patients with higher disease activity. Receiver operating curve analyses revealed fair discriminative power for active disease. Our results suggest a utility for netrin-1 as a novel biomarker for detecting disease activity in spondyloarthritis, for the first time to the best of our knowledge.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157055"},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/j.cyto.2025.157051
Chao huang, Bingjun Liang, Weizeng Shen
Objective
Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.
Methods
Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.
Results
A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (P < 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (R = 0.79, P < 0.001). High expression of COL1A1 tended to reduce overall survival (P = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (P < 0.05).
Conclusion
The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.
{"title":"PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway","authors":"Chao huang, Bingjun Liang, Weizeng Shen","doi":"10.1016/j.cyto.2025.157051","DOIUrl":"10.1016/j.cyto.2025.157051","url":null,"abstract":"<div><h3>Objective</h3><div>Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.</div></div><div><h3>Methods</h3><div>Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.</div></div><div><h3>Results</h3><div>A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (<em>P</em> < 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (<em>R</em> = 0.79, <em>P</em> < 0.001). High expression of COL1A1 tended to reduce overall survival (<em>P</em> = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157051"},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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