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}
Pub Date : 2025-10-13DOI: 10.1016/j.cyto.2025.157056
Lingshu Luan , Liuyang Lu , Li Xu , Wanming Chen , Qing Tian , Xiaobin Zhang , Haidong Yang
Background
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).
Methods
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).
Results
VEGF levels were significantly lower in TRS versus controls (P < 0.001), with no significant difference between TRS-CMS (P = 0.053) or CMS-controls (P = 0.051). NRG1β1 was significantly reduced in both TRS (P = 0.003) and CMS (P < 0.001) groups compared to controls. Neuropilin-1 decreased significantly only in the TRS group versus controls (P = 0.029). No significant difference was observed in S100B and S100A8 levels across all groups (all P > 0.05). Correlation analysis revealed a negative association between NRG1β1 levels and positive scores (r = −0.355, P = 0.014), and a significant positive correlation between VEGF levels and language function (r = 0.313, P = 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, P = 0.021).
Conclusion
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.
背景:血管内皮生长因子(VEGF)、神经调节蛋白-1 (NRG1)和神经匹林-1是重要的神经营养因子,参与神经发育、突触可塑性和精神分裂症病理生理相关的神经保护过程。本研究旨在探讨这些标志物在男性难治性精神分裂症(TRS)和慢性药物性精神分裂症(CMS)患者中的表达模式及其临床意义。方法:采用Luminex液悬芯片技术检测31例TRS患者、47例CMS患者和47例健康对照者血清中VEGF、NRG1β1、neuropilin-1、S100B、S100A8的水平。采用Positive and Negative Syndrome Scale (PANSS)和Repeatable Battery for Assessment of Neuropsychological Status (RBANS)评估精神症状和认知功能。结果:TRS组VEGF水平明显低于对照组(P < 0.05)。相关分析显示,CMS患者NRG1β1水平与阳性评分呈负相关(r = -0.355, P = 0.014), VEGF水平与语言功能呈显著正相关(r = 0.313, P = 0.032)。此外,VEGF在TRS患者中显示出潜在的保护作用(B = -1.098, RR = 0.333, 95% CI: 0.131-0.849, P = 0.021)。结论:VEGF可能是抗TRS的保护因子,其降低可能与治疗耐药有关。VEGF与语言功能之间的正相关表明其在认知过程中的作用,突出了其作为精神分裂症治疗生物标志物的潜力。
{"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 , Liuyang Lu , Li Xu , Wanming Chen , Qing Tian , Xiaobin Zhang , 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> < 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 < 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> > 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}
Pub Date : 2025-10-13DOI: 10.1016/j.cyto.2025.157054
Seok Woo Hong , Jeong-Hwa Baek , Kyung Jae Yoon , Jeong-Hyun Kang
Background
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).
Methods
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.
Results
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.
Conclusions
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.
{"title":"Diagnostic potential of immune serum proteins in Osteosaropenia identified via proximity extension assay","authors":"Seok Woo Hong , Jeong-Hwa Baek , Kyung Jae Yoon , 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}
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 (n = 15) and age- and sex-matched healthy controls (n = 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.
{"title":"Unveiling the role of trace elements in modulating inflammatory and oxidative pathways in CAG repeat–driven spinocerebellar ataxia","authors":"Surbhi Singh , Deepika Joshi , Abhay Kumar Yadav , Shani Vishwakarma , Janki Makani , Janhavi Yadav , Anil Kumar Maurya , Gulabi Yadav , Chandmayee Mohanty , Anand Kumar , 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}
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.
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.
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.
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.
{"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 , Fudan Huang , Shaik Althaf Hussain , 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}
Pub Date : 2025-10-09DOI: 10.1016/j.cyto.2025.157040
B.C. Wang , S. Chaki , H. Taufiq , K. Sikder , S.K. Shukla , K. Rafiq
Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (-/-) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation.
Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges.
These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.
{"title":"Sepsis-induced cardiac dysfunction: Gender bias role of allograft inflammatory factor-1","authors":"B.C. Wang , S. Chaki , H. Taufiq , K. Sikder , S.K. Shukla , K. Rafiq","doi":"10.1016/j.cyto.2025.157040","DOIUrl":"10.1016/j.cyto.2025.157040","url":null,"abstract":"<div><div>Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (<sup>-/-</sup>) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation.</div><div>Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges.</div><div>These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157040"},"PeriodicalIF":3.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263707","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 : 2025-10-08DOI: 10.1016/j.cyto.2025.157047
Leonardo Lima Cardoso, Delva Fonseca Lamec Thyares, Ana Letícia Monteiro Fernandes, Rosália Santos Ferreira, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Fernanda Silva Almeida, Tatjana de Souza Lima Keesen
Leishmania infantum, the main causative agent of zoonotic visceral leishmaniasis, persists and proliferates within host monocytes and macrophages. Numerous studies have focused on developing innovative therapies, as conventional treatments are hampered by high toxicity, drug resistance, and relapse. In recent decades, anti-leishmanial immunotherapy — aimed at triggering or modulating the host's immune response — has gained momentum, with various immunomodulators being tested in experimental and clinical settings. However, achieving effective immunotherapy remains challenging, as it requires a delicate balance between enhancing protective, parasite-specific immune responses and avoiding harmful hyperinflammation. In this context, we evaluated quercetin, a natural flavonoid with reported immunomodulatory properties, alone and in combination with Amphotericin B (AmB), against Leishmania infantum promastigotes and during human monocyte infection. Infected and non-infected PBMCs were assessed for parasite viability and cytotoxicity; monocyte infection rates, reactive oxygen species (ROS), nitric oxide (NO) production, and cytokine profiles. Quercetin showed significant anti-promastigote activity and, in combination with AmB, enhanced parasite death, indicating synergistic effects. It also reduced monocyte infection rates, enhanced ROS production, and downregulated levels of IL-6, IL-10, and IL-17, without altering NO production. These findings support the concept of quercetin as a dual-action agent, exerting direct anti-leishmanial effects while fine-tuning the host immune response. By promoting beneficial immunological pathways and dampening potentially deleterious cytokines, quercetin exemplifies the “trapeze act” of immunotherapy, suggesting its potential as an adjuvant to conventional chemotherapy in visceral leishmaniasis.
{"title":"Quercetin enhances amphotericin B activity and regulates ROS and cytokine production in human monocytes infected by Leishmania infantum","authors":"Leonardo Lima Cardoso, Delva Fonseca Lamec Thyares, Ana Letícia Monteiro Fernandes, Rosália Santos Ferreira, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Fernanda Silva Almeida, Tatjana de Souza Lima Keesen","doi":"10.1016/j.cyto.2025.157047","DOIUrl":"10.1016/j.cyto.2025.157047","url":null,"abstract":"<div><div><em>Leishmania infantum</em>, the main causative agent of zoonotic visceral leishmaniasis, persists and proliferates within host monocytes and macrophages. Numerous studies have focused on developing innovative therapies, as conventional treatments are hampered by high toxicity, drug resistance, and relapse. In recent decades, anti-leishmanial immunotherapy — aimed at triggering or modulating the host's immune response — has gained momentum, with various immunomodulators being tested in experimental and clinical settings. However, achieving effective immunotherapy remains challenging, as it requires a delicate balance between enhancing protective, parasite-specific immune responses and avoiding harmful hyperinflammation. In this context, we evaluated quercetin, a natural flavonoid with reported immunomodulatory properties, alone and in combination with Amphotericin B (AmB), against <em>Leishmania infantum</em> promastigotes and during human monocyte infection. Infected and non-infected PBMCs were assessed for parasite viability and cytotoxicity; monocyte infection rates, reactive oxygen species (ROS), nitric oxide (NO) production, and cytokine profiles. Quercetin showed significant anti-promastigote activity and, in combination with AmB, enhanced parasite death, indicating synergistic effects. It also reduced monocyte infection rates, enhanced ROS production, and downregulated levels of IL-6, IL-10, and IL-17, without altering NO production. These findings support the concept of quercetin as a dual-action agent, exerting direct anti-leishmanial effects while fine-tuning the host immune response. By promoting beneficial immunological pathways and dampening potentially deleterious cytokines, quercetin exemplifies the “trapeze act” of immunotherapy, suggesting its potential as an adjuvant to conventional chemotherapy in visceral leishmaniasis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157047"},"PeriodicalIF":3.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256892","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}
Cytokines are increasingly incorporated in psychiatric research. While biobanking provides advantages for different study designs, long-term storage could degrade cytokine quality and introduce bias. To date, reports on cytokine stability are based on small sample sizes (n < 20) and do not address long-term (4+ years) storage effects. This article reports two studies evaluating IL-6 and TNF-α measurements in human plasma samples biobanked for long periods. In the first study, with samples stored between 5 and 139 months (11.6 years), IL-6 concentrations were not significantly correlated with storage length in all available baseline data of the Signature Biobank (n[IL-6] = 1206, n[TNF-α] = 1223). TNF-α correlated negatively with storage length (r = −0.217; p < 0.001) indicating a decrease of concentrations with longer storage. In the second study, IL-6 and TNF-α concentrations were measured twice in the same plasma samples of 50 psychiatric participants from the Signature Biobank stored between analyses from 32 to 45 months. We assessed if storage effects differed between analytes. In IL-6, we observe a relatively good stability in samples stored up to 6 years. For TNF-α, we observed only a moderate stability of measurements (rTNF-α = 0.59; rIL-6 = 0.71) with linear decrease over time. As a potential solution, a corrective equation extracted from Study 1 was applied to TNF-α in the Study 2 sample; however, this did not improve correlation coefficients but might be useful in other settings. Integrating samples' age in statistical analyses and/or more systematic quality controls could mitigate degradation process.
{"title":"Long-term storage stability of plasma TNF-α and IL-6 concentrations of psychiatric emergency patients: The Signature Biobank","authors":"Enzo Cipriani , Charles-Édouard Giguère , Cécile Le Page , Helen Findlay , Janick Boissoneault , Stéphane Potvin , Robert-Paul Juster","doi":"10.1016/j.cyto.2025.157033","DOIUrl":"10.1016/j.cyto.2025.157033","url":null,"abstract":"<div><div>Cytokines are increasingly incorporated in psychiatric research. While biobanking provides advantages for different study designs, long-term storage could degrade cytokine quality and introduce bias. To date, reports on cytokine stability are based on small sample sizes (<em>n</em> < 20) and do not address long-term (4+ years) storage effects. This article reports two studies evaluating IL-6 and TNF-α measurements in human plasma samples biobanked for long periods. In the first study, with samples stored between 5 and 139 months (11.6 years), IL-6 concentrations were not significantly correlated with storage length in all available baseline data of the Signature Biobank (n[IL-6] = 1206, n[TNF-α] = 1223). TNF-α correlated negatively with storage length (<em>r</em> = −0.217; <em>p</em> < 0.001) indicating a decrease of concentrations with longer storage. In the second study, IL-6 and TNF-α concentrations were measured twice in the same plasma samples of 50 psychiatric participants from the Signature Biobank stored between analyses from 32 to 45 months. We assessed if storage effects differed between analytes. In IL-6, we observe a relatively good stability in samples stored up to 6 years. For TNF-α, we observed only a moderate stability of measurements (rTNF-α = 0.59; rIL-6 = 0.71) with linear decrease over time. As a potential solution, a corrective equation extracted from Study 1 was applied to TNF-α in the Study 2 sample; however, this did not improve correlation coefficients but might be useful in other settings. Integrating samples' age in statistical analyses and/or more systematic quality controls could mitigate degradation process.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157033"},"PeriodicalIF":3.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249116","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}