Cytokine最新文献

{"title":"Unveiling IL-41: A novel biomarker for polymyositis and dermatomyositis diagnosis","authors":"Zhi Li ,&nbsp;Wen Qin ,&nbsp;Xiudi Wu ,&nbsp;Mingcai Li ,&nbsp;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> &lt; 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}

{"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 ,&nbsp;Sho Ishigaki ,&nbsp;Mitsuhiro Akiyama ,&nbsp;Keiko Yoshimoto ,&nbsp;Waleed Alshehri ,&nbsp;Kanako Shimanuki ,&nbsp;Koichi Saito ,&nbsp;Hiroshi Takei ,&nbsp;Noriyasu Seki ,&nbsp;Hideto Tsujimoto ,&nbsp;Kenji Chiba ,&nbsp;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> &lt; 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 &gt;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}

{"title":"First-trimester prediction of gestational diabetes mellitus using resistin, chemerin, progranulin, omentin, and IL-10","authors":"Huriye Ezveci ,&nbsp;Sukran Dogru ,&nbsp;Fikriye Karanfil Yaman ,&nbsp;Pelin Bahçeci ,&nbsp;Hatice Bedia Yildiz ,&nbsp;Meltem Uyaner Kan ,&nbsp;İbrahim Kilinç ,&nbsp;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> &gt; 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}

{"title":"Serum IL-6 levels correlate with surgical stress factors in newborns with congenital diaphragmatic hernia","authors":"Takao Kobayashi ,&nbsp;Sota Iwatani ,&nbsp;Toshihiko Ikuta,&nbsp;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>_<em>s</em> = −0.610) and positively with intra-operative blood loss and 24-h post-operative transfusion volumes (<em>r</em>_<em>s</em> = 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}

{"title":"The relationship of plasma netrin-1 level with disease activity and other parameters in patients with axial spondyloarthritis","authors":"Fatih Serdar Baykal ,&nbsp;Serdar Can Güven ,&nbsp;Ahmet Kor ,&nbsp;Funda Eren ,&nbsp;Salim Neşelioğlu ,&nbsp;Bünyamin Polat ,&nbsp;Serdar Esmer ,&nbsp;Berkan Armağan ,&nbsp;Kevser Orhan ,&nbsp;İsmail Doğan ,&nbsp;Yüksel Maraş ,&nbsp;Salih Başer ,&nbsp;Özcan Erel ,&nbsp;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}

{"title":"PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway","authors":"Chao huang,&nbsp;Bingjun Liang,&nbsp;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> &lt; 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> &lt; 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> &lt; 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}

{"title":"Decreased serum VEGF, NRG1, and Neuropilin-1 levels in male patients with treatment-resistant schizophrenia: implications for VEGF as a protective factor","authors":"Lingshu Luan ,&nbsp;Liuyang Lu ,&nbsp;Li Xu ,&nbsp;Wanming Chen ,&nbsp;Qing Tian ,&nbsp;Xiaobin Zhang ,&nbsp;Haidong Yang","doi":"10.1016/j.cyto.2025.157056","DOIUrl":"10.1016/j.cyto.2025.157056","url":null,"abstract":"<div><h3>Background</h3><div>Vascular endothelial growth factor (VEGF), Neuregulin-1 (NRG1), and Neuropilin-1 are important neurotrophic factors involved in neurodevelopment, synaptic plasticity, and neuroprotection processes implicated in schizophrenia pathophysiology. This study aimed to investigate the expression patterns of these markers and their clinical implications in male patients with treatment-resistant schizophrenia (TRS) and chronically medicated schizophrenia (CMS).</div></div><div><h3>Methods</h3><div>In this cross-sectional study, serum levels of VEGF, NRG1β1, neuropilin-1, S100B, and S100A8 were measured using the Luminex liquid suspension chip technology in 31 TRS patients, 47 CMS patients, and 47 healthy controls. Psychiatric symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).</div></div><div><h3>Results</h3><div>VEGF levels were significantly lower in TRS versus controls (<em>P</em> &lt; 0.001), with no significant difference between TRS-CMS (<em>P</em> = 0.053) or CMS-controls (<em>P</em> = 0.051). NRG1β1 was significantly reduced in both TRS (<em>P</em> = 0.003) and CMS (P &lt; 0.001) groups compared to controls. Neuropilin-1 decreased significantly only in the TRS group versus controls (<em>P</em> = 0.029). No significant difference was observed in S100B and S100A8 levels across all groups (all <em>P</em> &gt; 0.05). Correlation analysis revealed a negative association between NRG1β1 levels and positive scores (<em>r</em> = −0.355, <em>P</em> = 0.014), and a significant positive correlation between VEGF levels and language function (<em>r</em> = 0.313, <em>P</em> = 0.032) in CMS patients. Additionally, VEGF demonstrated potential protective properties in TRS patients (B = -1.098, RR = 0.333, 95 %CI: 0.131–0.849, <em>P</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>VEGF may serve as a protective factor against TRS, with its reduction possibly contributing to treatment resistance. The positive correlation between VEGF and language function suggests its role in cognitive processes, highlighting its potential as a biomarker in schizophrenia treatment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157056"},"PeriodicalIF":3.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290541","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}

{"title":"Diagnostic potential of immune serum proteins in Osteosaropenia identified via proximity extension assay","authors":"Seok Woo Hong ,&nbsp;Jeong-Hwa Baek ,&nbsp;Kyung Jae Yoon ,&nbsp;Jeong-Hyun Kang","doi":"10.1016/j.cyto.2025.157054","DOIUrl":"10.1016/j.cyto.2025.157054","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcopenia, characterized by coexistence of osteoporosis and sarcopenia, is influenced by immunological dysfunction and systemic inflammation, however their specific roles remain unclear. This study aimed to investigate inflammation-related serum profiles in osteosarcopenia using the Proximity Extension Assay (PEA).</div></div><div><h3>Methods</h3><div>Overall, 50 participants with a history of falls and fractures were recruited and classified into three groups, controls, sarcopenia, and osteosarcopenia. Oseteosarcopenia was diagnosed in individuals with both functional sarcopenia and osteoporosis. Functional sarcopenia was diagnosed according to the Korean Working Group on Sarcopenia guidelines. Osteoporosis was defined as a T-score of the areal bone mineral density (aBMD) of the femoral neck ≤ −2.5. Serum inflammatory protein levels were quantified using the Olink® PEA inflammation panel, targeting 92 proteins.</div></div><div><h3>Results</h3><div>Twenty inflammation-related proteins were identified as differentially expressed proteins (DEPs), and 33 proteins showed significant correlations with clinical measures of muscle function or aBMD of the total hip, femoral neck or lumbar spine. Weighted Gene Co-Expression Network Analysis (WGCNA) identified 27 proteins with significant module membership and contribution to group separation. Notably, four proteins, including SLAMF1, OPG, FGF-23, and CSF-1 were DEPs, significant in WGCNA, and correlated with clinical variables. Principal component analysis and heatmap analyses revealed osteosacropenia as a distinct entity, differing from sarcopenia and controls. Bioinformatics suggested that T cell modulation and tumor necrosis factor binding capacity play significant roles in osteosarcopenia development.</div></div><div><h3>Conclusions</h3><div>Osteosarcopenia exhibited unique immune-related profiles distinct from those of sarcopenia and controls, emphasizing the potential role of inflammation and adaptive immunity in its pathogenesis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157054"},"PeriodicalIF":3.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290578","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}

{"title":"Unveiling the role of trace elements in modulating inflammatory and oxidative pathways in CAG repeat–driven spinocerebellar ataxia","authors":"Surbhi Singh ,&nbsp;Deepika Joshi ,&nbsp;Abhay Kumar Yadav ,&nbsp;Shani Vishwakarma ,&nbsp;Janki Makani ,&nbsp;Janhavi Yadav ,&nbsp;Anil Kumar Maurya ,&nbsp;Gulabi Yadav ,&nbsp;Chandmayee Mohanty ,&nbsp;Anand Kumar ,&nbsp;Royana Singh","doi":"10.1016/j.cyto.2025.157050","DOIUrl":"10.1016/j.cyto.2025.157050","url":null,"abstract":"<div><div>Spinocerebellar ataxias are genetically inherited neurodegenerative disorders, primarily caused by CAG trinucleotide repeat expansions in genes. While these genetic mutations initiate disease onset, increasing evidence suggests that systemic factors, particularly trace element imbalance, oxidative stress, and immune dysregulation, play critical roles in disease progression. In this study, peripheral blood samples from genetically confirmed SCA patients (<em>n</em> = 15) and age- and sex-matched healthy controls (<em>n</em> = 18) were analyzed. Atomic Absorption Spectroscopy revealed significant alterations in plasma concentrations of both essential and toxic trace elements, suggesting their involvement in neurotoxicity, redox imbalance, and inflammation. To explore these links, oxidative stress markers, including malondialdehyde, superoxide dismutase, and glutathione peroxidase, as well as cytokines such as interleukin-6, interleukin-4, and interleukin-10, were quantified using ELISA. Receiver operating characteristic analysis demonstrated high diagnostic accuracy of these markers, particularly GPx and IL-10. A strong interconnection was observed among trace element dysregulation, oxidative stress, and inflammatory responses, indicating a synergistic role in exacerbating neurodegeneration. Molecular docking revealed that abnormal trace element levels may impair antioxidant enzyme function by disrupting metal-binding interactions, offering mechanistic insight into enzymatic dysfunction. Bioinformatics analyses, including functional enrichment and protein–protein interaction mapping, identified significant associations with mitochondrial dysfunction, reactive oxygen species metabolism, and cytokine signaling pathways. These findings suggest that SCA pathogenesis is not driven by genetic mutation alone. The combined effects of trace element imbalance, oxidative stress, and inflammation contribute to a complex pathogenic network, reinforcing the importance of targeting both genetic and systemic factors in therapeutic strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157050"},"PeriodicalIF":3.7,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278592","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}

{"title":"Anakinra ameliorates insulin resistance and inflammation in a murine model of gestational diabetes through downregulation of Th17 responses Anakinra for the treatment of GDM in mice","authors":"Lingyan Zhang ,&nbsp;Fudan Huang ,&nbsp;Shaik Althaf Hussain ,&nbsp;Yi Tian","doi":"10.1016/j.cyto.2025.157039","DOIUrl":"10.1016/j.cyto.2025.157039","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is associated with low-grade inflammation which can contribute to insulin resistance and dysregulated glucose metabolism. Anakinra is a recombinant form of IL-1 receptor antagonist (IL-1Ra) that has shown promise in the control of several inflammatory diseases. The present study aimed to evaluate the potential of Anakinra in the control of inflammation and glucose metabolism in a genetic model of GDM.</div><div>Pregnant C57BL/KsJdb/+ (db/+) mice were used as the murine model of GDM and the glucose metabolism, insulin resistance as well as levels of inflammatory mediators were evaluated. The populations of Th17 and Treg cells were also analyzed in spleens of mice. Some GDM-associated parameters were studied in offspring along with an evaluation of oxidative stress in the liver and placenta.</div><div>Anakinra improved the glucose tolerance and insulin sensitivity of GDM mice and controlled the weight gain of the pregnant mice. The population of Th17 cells as key mediators of inflammatory processes declined in the Anakinra-received mice and the serum levels of pro-inflammatory cytokines as well as the activation of the NF-κB pathway declined accordingly. Besides, the infiltration of T-cells into the placenta was diminished in Anakinra-treated mice.</div><div>Anakinra demonstrated a potential for control of GDM by targeting low-grade inflammation and improving glucose metabolism. Regarding the fair properties of small molecules that render them suitable therapeutic tools, Anakinra might be a candidate therapeutic for the control of GDM more efficiently.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157039"},"PeriodicalIF":3.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263708","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}