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The role of cellular senescence in the pathogenesis of Rheumatoid Arthritis: Focus on IL-6 as a target gene 细胞衰老在类风湿关节炎发病机制中的作用:关注作为靶基因的 IL-6
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-25 DOI: 10.1016/j.cyto.2024.156762
Fengxia Xu , Zhen Li , Tao Liu , Xue Pang , Chang Fan , Hui Jiang
{"title":"The role of cellular senescence in the pathogenesis of Rheumatoid Arthritis: Focus on IL-6 as a target gene","authors":"Fengxia Xu ,&nbsp;Zhen Li ,&nbsp;Tao Liu ,&nbsp;Xue Pang ,&nbsp;Chang Fan ,&nbsp;Hui Jiang","doi":"10.1016/j.cyto.2024.156762","DOIUrl":"10.1016/j.cyto.2024.156762","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis is a chronic autoimmune disease. However, the specific role of senescence in rheumatoid arthritis (RA) is unknown. This study aimed to identify potential aging-related genes that have diagnostic and therapeutic value for RA.</div></div><div><h3>Methods</h3><div>The GSE89408 dataset was downloaded from the Gene Expression Omnibus (GEO). Aging-related genes were downloaded from the HAGR database. Differentially expressed genes (DEGs) were subsequently identified with the “edgeR” tool. Next, hub genes were identified with a PPI network and CytoHubba analysis. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of these hub genes. Immune infiltration analysis was performed with the CIBERSORT algorithm. Additionally, molecular docking was performed with CB-Dock2. Finally, correlation experiments were performed to validate the bioinformatics and molecular docking results.</div></div><div><h3>Results</h3><div>A total of 22 ADEGs were identified. Combined PPI network and CytoHubba analyses identified a total of 7 hub genes, including IL-6, IL7R, IL2RG, CDK1, PTGS2, and LEP, which are associated mainly with inflammation and immune responses. ROC analysis revealed that the hub genes were highly predictive of RA. Analysis of immune infiltration revealed that the 6 hub genes were positively associated with M1 macrophages. Validation experiments revealed that the inhibition of IL-6 significantly decreased the degree of synovial fibroblast (FLS) senescence. Furthermore, molecular docking and validation experiments revealed that IL-6 is a potential target for drug therapy.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that RA-FLS senescence may promote the development of RA via inflammatory and immune mechanisms. Seven hub genes were identified, of which IL-6 is a reliable biomarker for the diagnosis and treatment of RA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156762"},"PeriodicalIF":3.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319133","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}
引用次数: 0
The assessment of usefulness of cytokines and other soluble mediators as the predictors of sequalae development in various forms of tick-borne encephalitis (TBE) 评估细胞因子和其他可溶性介质作为各种蜱传脑炎(TBE)后遗症发展预测因子的作用
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-25 DOI: 10.1016/j.cyto.2024.156767
Piotr Czupryna , Anna Moniuszko-Malinowska , Gabriela Trojan , Justyna Adamczuk , Diana Martonik , Anna Parfieniuk-Kowerda , Ewelina Kruszewska , Maciej Giecko , Sambor Grygorczuk
{"title":"The assessment of usefulness of cytokines and other soluble mediators as the predictors of sequalae development in various forms of tick-borne encephalitis (TBE)","authors":"Piotr Czupryna ,&nbsp;Anna Moniuszko-Malinowska ,&nbsp;Gabriela Trojan ,&nbsp;Justyna Adamczuk ,&nbsp;Diana Martonik ,&nbsp;Anna Parfieniuk-Kowerda ,&nbsp;Ewelina Kruszewska ,&nbsp;Maciej Giecko ,&nbsp;Sambor Grygorczuk","doi":"10.1016/j.cyto.2024.156767","DOIUrl":"10.1016/j.cyto.2024.156767","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of the study was to assess the usefulness of cytokines and other soluble mediators in differentiation between severe and mild course of tick-borne encephalitis (TBE) as well as the predictor of sequalae development.</div></div><div><h3>Material and methods</h3><div>122 patients (mean age 47.66 ± 14.77 years, 43 females, 79 males) with TBE were included in the study.</div><div>Concentrations of 82 cytokines, growth factors, selectins, matrix metalloproteinases and other soluble mediators were measured in serum and CSF samples according to the manufacturer’s instruction on a Bio-Plex 200 System using the custom made Luminex assays. Enzyme-linked immunosorbent assays for the quantitative detection of human IL-26, IL-29 IL-22, CXCL12 were performed.</div></div><div><h3>Results</h3><div>No significant differences between serum concentrations of examined factors between group with sequelae and group with complete recovery were observed.</div><div>In the CSF the concentrations of GM-CSF, Il-1α, Il-2, Il-4, Il-6, Il-12p70, Il-17A, CXCL1, CXCL6, Il-8, CCL4, CCL20, TRAIL, CD40L, MMP8 were significantly higher in patients who developed sequelae than in patients with complete recovery.</div><div>For TRAIL concentration over 26.65 pg/ml in CSF the probability of sequalae development was 10.5 higher. In case of CCL20 – the concentration over 21.38 pg/ml in CSF the odds ratio was 6.429 times. For MMP-8 over 4210.54 pg/ml, the odds ratio was 11.222 times.</div></div><div><h3>Conclusions</h3><div>TRAIL, CCL-20 and MMP-8 are promising biomarkers of prediction of the sequalae development of TBE.</div><div>Pro-inflammatory cytokines IL-8, IL-1, IL-2, IL-12, IL-17A also associate well with the risk of sequelae and could be further evaluated as prognostic markers in TBE, individually or as elements of a larger model.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156767"},"PeriodicalIF":3.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319132","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}
引用次数: 0
Skin wound repairing effects of adipose mesenchymal stem cells is promoted by the combined application of insulin-like growth factor 1: The key role of miR-21-5p-mediated signaling transduction 联合应用胰岛素样生长因子1促进脂肪间充质干细胞的皮肤伤口修复效应:miR-21-5p介导的信号转导的关键作用
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-23 DOI: 10.1016/j.cyto.2024.156760
Shuo Cui , Linlei Wang , Huafei Zhao , Fei Lu , Yuhua Chen , Yadong Gu
{"title":"Skin wound repairing effects of adipose mesenchymal stem cells is promoted by the combined application of insulin-like growth factor 1: The key role of miR-21-5p-mediated signaling transduction","authors":"Shuo Cui ,&nbsp;Linlei Wang ,&nbsp;Huafei Zhao ,&nbsp;Fei Lu ,&nbsp;Yuhua Chen ,&nbsp;Yadong Gu","doi":"10.1016/j.cyto.2024.156760","DOIUrl":"10.1016/j.cyto.2024.156760","url":null,"abstract":"<div><div>Mesenchymal stem cells (ADMSCs) have been applied to the treatment of skin injuries and the co-administration of cytokines can enhance the effects. In the current study, the promoting effects of insulin-like growth factor 1 (IGF-1) on the skin wound healing effects of adipose-derived MSCs (ADMSCs) were assessed and the associated mechanism was explored by focusing on miR-21-5p mediated pathways. ADMSCs were isolated from epididymis rats, and skin wounded rats were employed as the <em>in vivo</em> model for evaluating the effect of ADMCs on skin healing and secretion of cytokines. Then a microarray assay was employed to select potential miR target of IGF-1 on ADMSCs. The level of the selected miR was modulated in ADMSCs, and the effects on skin injuries were also assessed. Administration of ADMSCs promoted skin wound healing and induced the production of bFGF, IL-1β, PDGF, SDF-1, IGF-1, and TNF-α. The co-administration of IGF-1 and ADMSCs strengthened the effect of ADMSCs on skin wound by suppressing activity of matrix metalloproteinase-1 (MMP-1). At molecular level, the treatment of IGF-1 up-regulated miR-21-5p level in ADMSCs, which then suppressed the expression of KLF6 in injured skin tissues and promoted wound healing. The inhibition of miR-21-5p counteracted the promoting effects of IGF-1 on the skin healing effects of ADMSCs. Findings outlined in the current study indicated that IGF-1 could promote the wound healing effects of ADMSCs by up-regulating miR-21-5p level.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156760"},"PeriodicalIF":3.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311180","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}
引用次数: 0
Zinc pathogenic importance in correcting immunity and restoring public health in the post-COVID period: An overview 锌致病剂在后 COVID 时期纠正免疫和恢复公众健康方面的重要性:概述
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-21 DOI: 10.1016/j.cyto.2024.156761
Maria Sankova , Vladimir Nikolenko , Marine Oganesyan , Yurii Vinnik , Liliya Gavryushova , Sofya Redina , Negorya Rizaeva , Aleksey Sankov , Kirill Bulygin , Andzhela Vovkogon , André Pontes-Silva , Yury Zharikov
{"title":"Zinc pathogenic importance in correcting immunity and restoring public health in the post-COVID period: An overview","authors":"Maria Sankova ,&nbsp;Vladimir Nikolenko ,&nbsp;Marine Oganesyan ,&nbsp;Yurii Vinnik ,&nbsp;Liliya Gavryushova ,&nbsp;Sofya Redina ,&nbsp;Negorya Rizaeva ,&nbsp;Aleksey Sankov ,&nbsp;Kirill Bulygin ,&nbsp;Andzhela Vovkogon ,&nbsp;André Pontes-Silva ,&nbsp;Yury Zharikov","doi":"10.1016/j.cyto.2024.156761","DOIUrl":"10.1016/j.cyto.2024.156761","url":null,"abstract":"<div><p>Context: The problem of correcting immune system function and compensating for co-morbidities becomes particularly clinically significant in the post-COVID period. There is evidence that certain trace elements in the human body, particularly zinc ions, play a critical role in restoring the function of the immune system and internal organs. Objective: To analyze the mechanisms of zinc action maintaining the body homeostasis in order to justify pathogenetically the inclusion of zinc drugs in the therapy of patients in the post-COVID period. Methods: Data from Elsevier, Global Health, PubMed-NCBI, Embase, MEDLINE, Scopus, Research gate, RSCI Scopus, Cochrane Library, Google Academy, e-LIBRARY.RU and CyberLeninka were used. Results: This review showed that the importance of zinc in maintaining body homeostasis in the post-COVID period is determined by its multifaceted effect on all parts of the immune system, its anti-inflammatory activity, antimicrobial properties and participation in the restoration of internal organ function. Elimination of zinc deficiency in the post-COVID period is essential to support immunity, compensate for comorbidities and reduce the risk of complications. The impossibility of synthesizing zinc in the body requires its constant intake in sufficient quantities. Zinc levels are significantly reduced after infectious diseases, as this element is specifically distributed to organs and tissues to maintain immunological and metabolic functions. The degree of zinc deficiency is associated with the severity of COVID-19 and the post-COVID period. It is pathogenetically justified to prescribe zinc drugs in the post-COVID period, the choice of which should take into account comorbidities and severity of hypozincemia. Conclusion: Regularly administered therapy with zinc drugs in the post-COVID period will help correct the population immunity and restore public health.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156761"},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271945","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}
引用次数: 0
Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation 加利福尼亚教师研究中女性接触全氟和多氟烷基物质 (PFAS) 与免疫反应之间的关系:横断面评估
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-18 DOI: 10.1016/j.cyto.2024.156753
Emily L. Cauble , Peggy Reynolds , Marta Epeldegui , Syam S. Andra , Larry Magpantay , Srinivasan Narasimhan , Divya Pulivarthi , Julie Von Behren , Otoniel Martinez-Maza , Debbie Goldberg , Emma S. Spielfogel , James V. Lacey Jr. , Sophia S. Wang
{"title":"Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation","authors":"Emily L. Cauble ,&nbsp;Peggy Reynolds ,&nbsp;Marta Epeldegui ,&nbsp;Syam S. Andra ,&nbsp;Larry Magpantay ,&nbsp;Srinivasan Narasimhan ,&nbsp;Divya Pulivarthi ,&nbsp;Julie Von Behren ,&nbsp;Otoniel Martinez-Maza ,&nbsp;Debbie Goldberg ,&nbsp;Emma S. Spielfogel ,&nbsp;James V. Lacey Jr. ,&nbsp;Sophia S. Wang","doi":"10.1016/j.cyto.2024.156753","DOIUrl":"10.1016/j.cyto.2024.156753","url":null,"abstract":"<div><h3>Introduction</h3><p>Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that have been linked to a number of health outcomes, including those related to immune dysfunction. However, there are limited numbers of epidemiological-based studies that directly examine the association between PFAS exposure and immune responses.</p></div><div><h3>Methods</h3><p>In this cross-sectional study nested in the California Teachers Study cohort, we measured nine PFAS analytes in serum. Of the 9 analytes, we further evaluated four (PFHxS [perfluorohexane sulfonate], PFNA [perfluorononanoic acid], PFOA [perfluorooctanoic acid], PFOS [perfluorooctanesulfonic acid]) that had detection levels of &gt; 80 %, in relation to 16 systemic inflammatory/immune markers and corresponding immune pathways (Th1 [pro-inflammatory/macrophage activation], B-cell activation, and T-cell activation). Study participants (n = 722) were female, completed a questionnaire regarding various health measures and behaviors, and donated a blood sample between 2013–2016. The association between PFAS analytes and individual immune markers and pathways were evaluated by calculating odds ratios (OR) and 95 % confidence intervals (CI) in a logistic regression model. PFAS analytes were evaluated both as a dichotomous exposure (above or below the respective median) and as a continuous variable (per 1 unit increase [ng/mL]).</p></div><div><h3>Results</h3><p>The prevalence of detecting any PFAS analyte rose with increasing age, with the highest PFAS prevalence observed among those aged 75 + years and the lowest PFAS prevalence observed among those aged 40–49 years (study participant age range: 40–95 years). Significant associations with BAFF (B-cell activating factor) levels above the median were observed among participants with elevated (defined as above the median) levels of PFHxS (OR=1.53), PFOA (OR=1.43), and PFOS (OR=1.40). Similarly, there were statistically significant associations between elevated levels of PFHxS and TNFRII (tumor necrosis factor receptor 2) levels (OR=1.78) and IL2Rα (interleukin 2 receptor subunit alpha) levels (OR=1.48). We also observed significant inverse associations between elevated PFNA and sCD14 (soluble cluster of differentiation 14) (OR=0.73). No significant associations were observed between elevated PFNA and any immune marker. Evaluation of PFAS exposures as continuous exposures in association with dichotomized cytokines were generally consistent with the dichotomized associations.</p></div><div><h3>Conclusions</h3><p>PFAS exposure was associated with altered levels of circulating inflammatory/immune markers; the associations were specific to PFAS analyte and immune marker. If validated, our results may suggest potential immune mechanisms underlying associations between the different PFAS analytes and adverse health outcomes.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156753"},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043466624002576/pdfft?md5=8df70d8434ceffdffcbc9b3c792bf5e5&pid=1-s2.0-S1043466624002576-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238976","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}
引用次数: 0
Old drug, new use: Recent advances for G-CSF 老药新用:G-CSF 的最新进展
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156759
Lun Yan , Jing Li , Yang Yang , Xi Zhang , Cheng Zhang
{"title":"Old drug, new use: Recent advances for G-CSF","authors":"Lun Yan ,&nbsp;Jing Li ,&nbsp;Yang Yang ,&nbsp;Xi Zhang ,&nbsp;Cheng Zhang","doi":"10.1016/j.cyto.2024.156759","DOIUrl":"10.1016/j.cyto.2024.156759","url":null,"abstract":"<div><p>Granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3 (CSF3), is a proinflammatory cytokine that primarily stimulates the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils. Over the past years, G-CSF has mainly been used to cure patients with neutropenia and as a part of chemotherapy to induct the remission for refractory/relapse leukemia. Recent studies showed that C-CSF can been used as condition regimens and as a part of preventive methods after allogeneic transplantation to improve the survival of patients and also has immunoregulation, and has promote or inhibit the proliferation of solid tumors. Therefore, in this review, we firstly describe the structure for G-CSF. Then its functions and mechanism were reviewed including the neutrophil mobilization, differentiation, migration, and inhibiting apoptosis of neutrophils, and its immunoregulation. Finally, the clinical applications were further discussed.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156759"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238977","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}
引用次数: 0
IL-33/ST2 enhances MMP-12 expression by macrophages to mediate inflammatory and immune response in IgG4-Related Ophthalmic Disease IL-33/ST2 可增强巨噬细胞 MMP-12 的表达,从而介导 IgG4 相关眼病的炎症和免疫反应
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156754
Xia Ding , Yu Yu , Dai Su , Ming Lin , Mingjiao Chen , Yue Xing , Jin Li
{"title":"IL-33/ST2 enhances MMP-12 expression by macrophages to mediate inflammatory and immune response in IgG4-Related Ophthalmic Disease","authors":"Xia Ding ,&nbsp;Yu Yu ,&nbsp;Dai Su ,&nbsp;Ming Lin ,&nbsp;Mingjiao Chen ,&nbsp;Yue Xing ,&nbsp;Jin Li","doi":"10.1016/j.cyto.2024.156754","DOIUrl":"10.1016/j.cyto.2024.156754","url":null,"abstract":"<div><p>IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the Lat<sup>Y136F</sup> mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12<sup>+</sup> cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156754"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043466624002588/pdfft?md5=c903debe55196987d128569a776777fc&pid=1-s2.0-S1043466624002588-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239017","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}
引用次数: 0
Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells 优化 CAR-T 细胞培养:IL-2、IL-12 和 IL-21 对 CAR-T 细胞的不同影响
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156758
Mengmeng Zhang , JingJing Kong , Fanxiang Yin , Jianxiang Shi , Jin Li , Zan Qiu , Baohong Yue , Shuya Wang , Nannan Sun , Quande Lin , Liyan Fu , Xiaoqian Wang , Xianlei Sun , Yanxia Gao , Yong Jiang , Rongqun Guo
{"title":"Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells","authors":"Mengmeng Zhang ,&nbsp;JingJing Kong ,&nbsp;Fanxiang Yin ,&nbsp;Jianxiang Shi ,&nbsp;Jin Li ,&nbsp;Zan Qiu ,&nbsp;Baohong Yue ,&nbsp;Shuya Wang ,&nbsp;Nannan Sun ,&nbsp;Quande Lin ,&nbsp;Liyan Fu ,&nbsp;Xiaoqian Wang ,&nbsp;Xianlei Sun ,&nbsp;Yanxia Gao ,&nbsp;Yong Jiang ,&nbsp;Rongqun Guo","doi":"10.1016/j.cyto.2024.156758","DOIUrl":"10.1016/j.cyto.2024.156758","url":null,"abstract":"<div><h3>Background</h3><p>Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive.</p></div><div><h3>Methods</h3><p>Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion.</p></div><div><h3>Results</h3><p>Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156758"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239018","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}
引用次数: 0
Lupeol stimulates iNOS, TNF-α, and IL-10 expression in the U937 cell line infected with old-world Leishmania donovani 羽扇豆醇能刺激感染了旧世界利什曼原虫的 U937 细胞系中 iNOS、TNF-α 和 IL-10 的表达
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-16 DOI: 10.1016/j.cyto.2024.156757
Talib Fadhil Abbas , Hayder Z. Ali
{"title":"Lupeol stimulates iNOS, TNF-α, and IL-10 expression in the U937 cell line infected with old-world Leishmania donovani","authors":"Talib Fadhil Abbas ,&nbsp;Hayder Z. Ali","doi":"10.1016/j.cyto.2024.156757","DOIUrl":"10.1016/j.cyto.2024.156757","url":null,"abstract":"<div><h3>Objective</h3><p>Visceral leishmaniasis is a neglected tropical disease that can be lethal if not treated. The available medicines have severe side effects, such as toxicity and drug resistance. Various investigations are looking into new anti-leishmanial compounds from natural products that have little impact on host cells. Lupeol, a triterpenoid present in the flora of many edible plants, has been shown to have antimicrobial properties. The present study investigated the immunomodulatory effects of lupeol on U937 macrophages infected with <em>Leishmania donovani</em>, focusing on the expression of key cytokines and enzymes involved in the immune response.</p></div><div><h3>Methods</h3><p>U937 macrophages were infected with <em>Leishmania donovani</em> amastigotes and treated with varying concentrations of lupeol throughout three days. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were measured using real-time polymerase chain reaction (RT-PCR). A positive simulation of gene expression was estimated using ΔΔCT to assess relative expression.</p></div><div><h3>Results</h3><p>The results demonstrated that lupeol significantly upregulated iNOS and TNF-α expression, especially at higher concentrations, indicating enhanced pro-inflammatory and anti-leishmanial activity. Interestingly, IL-10 expression also increased, suggesting a complex immunomodulatory role of lupeol that involves both pro-inflammatory and anti-inflammatory pathways. Pearson correlation analysis revealed a strong association between iNOS and TNF-α (0.97692), as well as a moderate correlation between iNOS and IL-10 (0.51603).</p></div><div><h3>Conclusion</h3><p>These findings suggest that lupeol may promote a balanced immune response, enhancing the body’s ability to combat <em>L. donovani</em> while potentially mitigating excessive inflammation. Lupeol can potentially serve as a novel therapeutic agent against visceral leishmaniasis.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156757"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242837","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}
引用次数: 0
COVID 19: Prevention and treatment through the Indian perspective COVID 19:从印度角度看预防和治疗问题
IF 3.7 3区 医学
Cytokine Pub Date : 2024-09-15 DOI: 10.1016/j.cyto.2024.156756
Harish Chandra , Archana Yadav , Rajendra Prasad , Kalpana Sagar , Nitin Bhardwaj , Kartikey Kumar Gupta , Ghanshyam Singh Thakur , Manisha Nigam , Raffaele Pezzani , João Paulo Martins de Lima , Henrique Douglas Melo Coutinho , Abhay Prakash Mishra
{"title":"COVID 19: Prevention and treatment through the Indian perspective","authors":"Harish Chandra ,&nbsp;Archana Yadav ,&nbsp;Rajendra Prasad ,&nbsp;Kalpana Sagar ,&nbsp;Nitin Bhardwaj ,&nbsp;Kartikey Kumar Gupta ,&nbsp;Ghanshyam Singh Thakur ,&nbsp;Manisha Nigam ,&nbsp;Raffaele Pezzani ,&nbsp;João Paulo Martins de Lima ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Abhay Prakash Mishra","doi":"10.1016/j.cyto.2024.156756","DOIUrl":"10.1016/j.cyto.2024.156756","url":null,"abstract":"<div><p>The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019–2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"183 ","pages":"Article 156756"},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233859","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}
引用次数: 0
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