Cytokine最新文献

{"title":"The role of TNF in metabolic disorders and liver diseases","authors":"Chuze Xu ,&nbsp;Sohaib Hasan Abdullah Ezzi ,&nbsp;Xiaodi Zou ,&nbsp;Yanzhao Dong ,&nbsp;Ahmad Alhaskawi ,&nbsp;Haiying Zhou ,&nbsp;Vishnu Goutham Kota ,&nbsp;Mohamed Hasan Abdulla Hasan Abdulla ,&nbsp;Sahar Ahmed Abdalbary ,&nbsp;Hui Lu","doi":"10.1016/j.cyto.2025.156933","DOIUrl":"10.1016/j.cyto.2025.156933","url":null,"abstract":"<div><div>Tumor necrosis factor (TNF) is identified as a pro-inflammatory cytokine critical to the pathology of liver disease. In the carbohydrate metabolism, TNF has been demonstrated to impede the insulin signaling pathway, thereby precipitating glucose intolerance and insulin resistance. In lipid metabolism, TNF upregulates genes implicated in fatty acid synthesis, resulting in increased lipid accumulation within the liver. In amino acid metabolism, TNF has shown to promote the gene expression for amino acid catabolism, leading to decreased protein synthesis. Additionally, TNF stimulates the production of other chemokines and inflammatory cytokines that can further exacerbate liver injury. Overall, TNF is crucial in developing liver diseases by disrupting various metabolic pathways in the liver, causing insulin resistance, lipid accumulation, and decreased protein synthesis. This review summarizes the present understanding of TNF's role in the regulation of carbohydrate, lipid and amino acid metabolism in liver disease together with its potential therapeutic implications.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156933"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747949","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":"Progress of IL-10 and liver metastasis","authors":"Chuanfei Zeng ,&nbsp;Fengyuan Niu ,&nbsp;Huan Li,&nbsp;Ziyin Huang,&nbsp;Yujia Ke,&nbsp;Linxin Yu,&nbsp;Mingkai Chen","doi":"10.1016/j.cyto.2025.156932","DOIUrl":"10.1016/j.cyto.2025.156932","url":null,"abstract":"<div><div>Liver metastasis can occur in a wide range of cancers and have a significant impact on patient survival and prognosis. Once liver metastasis occurs, patients often lose the opportunity for surgery, and although a small percentage of patients can undergo hepatic resection to prolong survival, the benefit is not great. There were also many factors affecting liver metastasis, including reprogramming of the primary tumor metabolism, disturbances in the immune microenvironment and immune cells, alterations in the gut microbiota, and epigenetic changes. Interleukin-10 (IL-10) has a dual role as a cytokine that has been found in recent years to be pro-inflammatory as well as pro-liver metastasis. IL-10 exerts pro-metastatic effects mainly by regulating the polarization of tumor macrophages in the tumor microenvironment, especially by promoting the polarization of M2 macrophages. However, the role of IL-10 in tumorigenesis and progression remains controversial and the molecular mechanism involved in promoting liver metastasis is currently unclear. In view of the increasing role of IL-10 in promoting liver metastasis, this review summarizes the role of IL-10 in liver metastasis of colorectal cancer, breast cancer and other tumors in recent years, and provides ideas for subsequent clinical practice and basic research.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156932"},"PeriodicalIF":3.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739772","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":"Endothelial barrier disruptive effect of IFN-Ƴ and TNF-α: Synergism of pro-inflammatory cytokines","authors":"Chin Theng Ng ,&nbsp;Lai Yen Fong ,&nbsp;Jun Jie Tan ,&nbsp;Muhammad Nazrul Hakim Abdullah","doi":"10.1016/j.cyto.2025.156922","DOIUrl":"10.1016/j.cyto.2025.156922","url":null,"abstract":"<div><div>Crosstalk and synergy between interferon-γ (IFN-Ƴ) and tumor necrosis factor-α (TNF-α) in endothelial cells have previously been documented, however, there is an absence of articles reviewing the synergistic effect of IFN-Ƴ and TNF-α in regulating the endothelial barrier function. This review discusses the regulatory mechanisms and recent evidence of the synergism of IFN-γ and TNF-α in causing destabilization of endothelial junctions in various clinical studies and preclinical models. Articles were retrieved from electronic databases such as Web of Science, PubMed, Google Scholar, and Scopus. The search terms used were “interferon”, “interferon-gamma”, “tumor necrosis factor-α”, “vascular inflammation”, “endothelial barrier”, “endothelial permeability” and “synergism”. We selected articles published between 2004 and 2024. Through the Rho-associated protein kinase (ROCK) and p38 mitogen-activated protein (MAP) kinase pathways, our results showed that IFN-γ controls the remodeling of actin and the stability of junctions. In comparison to IFN-γ, the signaling cascades triggered by TNF-α involve a variety of pathways such as nuclear factor-kappa B (NF-κB), small GTPases, tyrosine kinases, integrin receptors, and barrier-stabilizing molecules such as Ras-related proteins 1A (Rap1A) and Rac family small GTPase 1 (Rac1). In the context of IFN-γ and TNF-α synergism, combined IFN-γ and TNF-α alter adherens and tight junctions. It is deduced that c-Jun N-terminal kinase (JNK), signal transducers and activators of transcription (STAT1), and caspase signaling pathways regulate endothelial barrier disruption caused by IFN-γ and TNF-α. Collectively, the mechanism underlying the synergistic action of IFN-γ and TNF-α is still lacking. Future work is needed to explore the crosstalk pathways of IFN-γ and TNF-α involved in the regulation of endothelial barrier function such as modulation of extracellular matrix (ECM) structure, involvement of tyrosine kinases and roles of small GTPases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156922"},"PeriodicalIF":3.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725946","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":"Tumor-educated Neutrophils Induce Epithelial-mesenchymal Transition and Metastasis in Colorectal Cancer Through Interleukin-17a Secretion","authors":"Yibing Gong ,&nbsp;Qingshuang Luo ,&nbsp;Haiqi Tan ,&nbsp;Jingyi Long ,&nbsp;Longtai Hu ,&nbsp;Moyed abd alhussain Hamza Al-saadawe ,&nbsp;Jinke Yao ,&nbsp;Xiaoming Lyu ,&nbsp;Lizhen Qiu ,&nbsp;Gongfa Wu","doi":"10.1016/j.cyto.2025.156928","DOIUrl":"10.1016/j.cyto.2025.156928","url":null,"abstract":"<div><div>The role of neutrophils in defending against infections and regulating immune responses is well-known. In cancer, tumor-associated neutrophils also play a significant role in the progression of tumors. However, the specific mechanisms of their interaction with human colorectal tumors have not been fully elucidated. Our study found that tumor-educated neutrophils can activate the STAT3 signaling pathway in colorectal cancer cells by secreting IL-17a. This leads to increased migration and invasion of colorectal cancer cells, promoting tumor growth by triggering epithelial-to-mesenchymal transition (EMT). These findings suggest that IL-17a secreted by tumor-educated neutrophils contributes to the development of colorectal cancer through the IL-17a/STAT3 signaling pathway. This provides new insights for potential treatments for colorectal cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156928"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725947","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":"Self-assembling sequentially administered tumor targeted Split IL-12p35 and p40 subunits to improve the therapeutic index of systemically delivered IL-12 therapy for cancer","authors":"P.S. Gurel,&nbsp;R.G. Newman,&nbsp;S. Pearson,&nbsp;K. Dreaden,&nbsp;C. Wang,&nbsp;S.S. Donatelli,&nbsp;Y. Zhao,&nbsp;J. Chamoun,&nbsp;J.F. Heiber","doi":"10.1016/j.cyto.2025.156912","DOIUrl":"10.1016/j.cyto.2025.156912","url":null,"abstract":"<div><div>IL-12, also called IL-12p70, is a highly potent, proinflammatory heterodimeric cytokine that can mediate many beneficial anti-tumor effects. In preclinical studies, recombinant IL-12, as well as IL-12 gene therapies, have demonstrated notable anti-tumor results across various tumor types; however, IL-12 clinical benefit has been limited by its poor tolerability at potentially efficacious doses. We have developed a novel approach to mitigate the toxicity of IL-12 by engineering tumor-targeted split IL-12 that preferentially localizes IL-12 activity to the tumor microenvironment. The functionally inactive IL-12 subunits, p35 and p40, are separately fused to antibody fragments targeting a highly expressed tumor-associated antigen, uPAR. The goal of this strategy is to drive assembly and activity of the IL-12 heterodimer into the tumor site through sequential administration of the targeted subunits, reducing systemic exposure and thereby potentially reducing associated toxicities. We use in vitro activity assays along with in vivo pharmacokinetic and pharmacodynamic studies in mice and non-human primates to demonstrate that the split IL-12 anti-uPAR fusions are capable of assembly and activity in vivo. The targeted p35 and p40 subunits are capable of complexing to form IL-12p70 and inducing STAT4 phosphorylation when applied to cultured immune cells, indicating in vitro IL-12 activity. Furthermore, sequential administration of subunits in in vivo mouse models demonstrates rapid serum clearance of IL-12 while extending retention in the tumor. Finally, dosing in non-human primates shows molecules are functionally active in vivo. This is a unique strategy with great clinical promise to harness the therapeutic potential of IL-12 while potentially avoiding the toxicity associated with systemic delivery.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156912"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LTK deficiency induces macrophage M2 polarization and ameliorates Sjogren's syndrome by reducing chemokine CXCL13","authors":"Xiuyuan Feng ,&nbsp;Junhui Lu ,&nbsp;Wei Cheng ,&nbsp;Ping Zhao ,&nbsp;Xin Chang ,&nbsp;Jian Wu","doi":"10.1016/j.cyto.2025.156905","DOIUrl":"10.1016/j.cyto.2025.156905","url":null,"abstract":"<div><h3>Background</h3><div>Sjogren's syndrome (SS) is an autoimmune disease involving macrophage infiltration of the exocrine glands. LTK, a receptor tyrosine kinase, is involved in many autoimmune diseases, such as lupus erythematosus. The objectives of this study was to explore the impact of LTK on autophagy in SS.</div></div><div><h3>Methods</h3><div>The NCBI Gene Expression Omnibus (GEO) database was used to screen for differentially expressed genes (DEGs) in SS patients and validated by quantitative reverse transcription PCR (RT-qPCR) in A253 cells with EGF and IFN-γ. Meanwhile, lentiviral vectors were used to transfect A253 cells for stable LTK silencing. CCK-8, flow cytometry, and transmission electron microscopy (TEM), Western blotting (WB) was employed to assess proliferation, apoptosis, autophagy, and autoimmune antigens (Ro52/SSA and La/SSB) in A253 cells. Then, macrophages were treated with 100 ng/ml of LPS to induce the polarization of macrophages towards the M1 phenotype, while macrophages were treated with IL-4 to activate the macrophage M2 phenotype. LTK-silenced A253 cells were co-cultured with macrophages. WB as well as flow cytometry were used to assess macrophage polarization markers. Furthermore, protein-antibody microarrays were utilized to analyze downstream proteins regulated by LTK. Finally, the functionality of LTK was confirmed in NOD/ShiLtJ mice.</div></div><div><h3>Results</h3><div>LTK expression in the GEO database was increased in SS patients. And LTK was also significantly increased by EGF and IFN-γ. Knockdown of LTK increased proliferation and autophagy in A253 cells. While LTK deficiency inhibited the expression of Ro52/SSA and La/SSB, and apoptosis in A253 cells. Furthermore, LTK-silenced A253 cells promoted polarization of macrophages towards the M2 phenotype, which is associated with the pathogenesis of SS. Knockdown of LTK resulted in reduced expression of CXCL13, which in turn triggered macrophage M2 polarization. Additionally, LTK deficiency ameliorated submandibular gland tissue damage and inhibited autoimmune antigens secretion in NOD/ShiLtJ mice. In addition, the expression of autophagy markers and M2 polarization markers in the submandibular gland tissue was increased by shLTK.</div></div><div><h3>Conclusion</h3><div>LTK could promote progressive SS pathogenesis via CXCL13. This discovery indicates that targeting LTK/CXCL13 could be a potential therapeutic strategy for the clinical management of SS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156905"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706515","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":"Exosomes derived from myelodysplastic syndromes cells induce IL-1β production from macrophages to promote disease progress","authors":"Peichun Li ,&nbsp;Dongmei Guan ,&nbsp;Shuo Li ,&nbsp;Ju Deng ,&nbsp;HongYu Zhang ,&nbsp;Xiaoli Liu ,&nbsp;Xiuhua Chen ,&nbsp;Zhifang Xu ,&nbsp;Hongwei Wang ,&nbsp;Fanggang Ren","doi":"10.1016/j.cyto.2025.156924","DOIUrl":"10.1016/j.cyto.2025.156924","url":null,"abstract":"<div><h3>Background</h3><div>Exosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular immunity.Our previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been elucidated.Macrophages are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS.</div></div><div><h3>Methods</h3><div>Changes in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell lines.After induction of human monocyte cell line (THP-1) into THP-1-Mφ macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (Mφ) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-Mφ to observe macrophage (Mφ) differentiation.Flow cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this process.Gene and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB.</div></div><div><h3>Results</h3><div>IL-1β levels were significantly higher in the peripheral blood of MDS patients compared to controls.The exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1β from THP-1-Mφ cells, and promote the proliferation, apoptosis and migration ability of MDS cell lines.Exosomes stimulate macrophages to produce IL-1β and promote MDS disease progression through the MER/ERK pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156924"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706514","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":"Aqueous humor mediator levels as biomarkers of anti-VEGF response in age-related macular degeneration","authors":"Stéphanie Baillif ,&nbsp;Sacha Nahon-Esteve ,&nbsp;Tanguy Pace-Loscos ,&nbsp;Gilles Pagès ,&nbsp;Maeva Dufies","doi":"10.1016/j.cyto.2025.156921","DOIUrl":"10.1016/j.cyto.2025.156921","url":null,"abstract":"<div><h3>Purpose</h3><div>To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response.</div></div><div><h3>Design</h3><div>Interventional, monocentric, prospective, clinical study.</div></div><div><h3>Participants</h3><div>Treatment-naïve nAMD patients.</div></div><div><h3>Methods</h3><div>Aqueous humor samples (100–200 μL) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1β, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1α and TNFα) using multiplex arrays.</div></div><div><h3>Main outcomes measures</h3><div>The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4.</div></div><div><h3>Results</h3><div>Fifteen eyes were included in the study. BCVA remained stable throughout the study (<em>p</em> = 0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (<em>p</em> &lt; 0.0001, p &lt; 0.0001, <em>p</em> &lt; 0.001 and p &lt; 0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p &lt; 0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels ≤50 pg/mL: they showed higher baseline IL-6 levels (<em>p</em> = 0.05), and elevated IL-6 (<em>p</em> = 0.03), PlGF (<em>p</em> = 0.02), VEGF-C (<em>p</em> = 0.005), IL-8 (<em>p</em> = 0.04), and TNFα (<em>p</em> = 0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (<em>p</em> = 0.007). Patients who required a fourth IVI within 8 weeks of the loading dose had higher baseline TNFα levels (<em>p</em> = 0.05); higher MIP-1α levels after the first IVI (<em>p</em> = 0.045); and elevated TNFα (<em>p</em> = 0.026) and IL-8 (<em>p</em> = 0.029) levels after the second IVI.</div></div><div><h3>Conclusions</h3><div>The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval &gt; 8 weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156921"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703910","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":"Longitudinal inflammatory biomarker profiling in intrauterine growth restricted preterm infants","authors":"Laura E. Lorenger ,&nbsp;Timothy J. Boly ,&nbsp;Rachael M. Hyland ,&nbsp;Jennifer R. Bermick","doi":"10.1016/j.cyto.2025.156916","DOIUrl":"10.1016/j.cyto.2025.156916","url":null,"abstract":"<div><h3>Objectives</h3><div>Intrauterine growth restriction (IUGR) places premature infants at an increased risk of multiple neonatal morbidities. Previous studies have found increased concentrations of pro-inflammatory biomarkers in IUGR infants at the time of birth and through the first postnatal month. This study aims to assess the longitudinal inflammatory profile of IUGR infants from birth to discharge from the neonatal intensive care unit.</div></div><div><h3>Materials and Methods</h3><div>A case-control study was performed with 24 IUGR infants and 24 appropriate for gestational age (AGA) infants born prematurely at or before 32 6/7 weeks' gestational age included. Residual clinical serum samples were collected and serum concentrations of IL-1β, sIL2Rα, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, and TNF-α were measured by multi-plex protein assay. Residual clinical whole blood samples were collected, peripheral mononuclear blood cells were isolated, and flow cytometry was performed to assess differences in populations of peripheral immune cells.</div></div><div><h3>Results</h3><div>There were significant differences in the birth weight and birth weight percentile between the IUGR and AGA groups, but no further demographic differences. The was significant elevation of IL-8, IL-10, and MCP-1 in the IUGR population at various timepoints during admission. There were no differences in overall cell populations between the two groups, however there were significantly increased activated classical monocytes and cytotoxic T cells in the IUGR group one month post-delivery.</div></div><div><h3>Conclusion</h3><div>Intrauterine growth restriction contributes to a fetal and continued neonatal pro-inflammatory state, as evidenced by elevation in IL-8 and MCP-1. Though there are increased populations of activated classical monocytes and cytotoxic T cells in these infants, this pro-inflammatory state may also contribute to tissue-specific inflammation which contributes to worsened neonatal outcomes for premature IUGR infants.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156916"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695999","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":"MiR-125b suppresses bladder Cancer cell growth and triggers apoptosis by regulating IL-6/IL-6R/STAT3 axis in vitro and in vivo","authors":"Fang Lin ,&nbsp;Shaorun Hu ,&nbsp;Jinxiang Chen ,&nbsp;Haiyang Li ,&nbsp;Mengting Li ,&nbsp;Rong Li ,&nbsp;Min Xu ,&nbsp;Mao Luo","doi":"10.1016/j.cyto.2025.156926","DOIUrl":"10.1016/j.cyto.2025.156926","url":null,"abstract":"<div><div>Bladder cancer (BLCA) is an aggressive malignancy characterized by limited therapeutic options and a poor prognosis. Research has indicated that abnormally expressed miRNAs play a significant role in the pathogenesis of BLCA, although the specific mechanisms remain unclear. MiR-125b plays a tumor suppressor role in a variety of cancers and affects the biological processes of cancer cells such as proliferation, invasion, migration and apoptosis by regulating different signaling pathways. Elucidation of the molecular mechanisms underlying miR-125b may provide clinical therapeutic strategies for bladder cancer. Here, miR-125b was downregulated whereas its targets IL-6R and STAT3 were upregulated in BLCA, as evidenced by bioinformatics analysis. Kaplan-Meier analysis confirmed that miR-125b serves as an independent prognostic factor linked to overall survival (OS) in patients with bladder cancer. Furthermore, overexpression of miR-125b significantly inhibited BLCA cell proliferation, migration, and invasion, while promoting apoptosis, as evidenced by an increased Bax/Bcl-2 ratio and activated cleaved caspase-3. Further investigations demonstrated that miR-125b directly targets and downregulates both IL-6R and STAT3. In a xenograft model, miR-125b overexpression effectively inhibited tumor growth in bladder cancer by blocking IL-6/IL-6R and STAT3 signaling pathways. Collectively, these findings broaden our understanding of the mechanism by which miR-125b acting as a BLCA suppressor in apoptotic regulation by targeting the IL-6/IL-6R/STAT3 signaling pathway, providing novel insights regarding the design of novel miRNA based therapeutic strategies against BLCA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156926"},"PeriodicalIF":3.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680563","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}