Cytokine最新文献

{"title":"Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.","authors":"Francois Dos Santos,&nbsp;Philip J. Steer,&nbsp;Mark R. Johnson","doi":"10.1016/j.cyto.2025.156886","DOIUrl":"10.1016/j.cyto.2025.156886","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GRO<em>α</em>, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.</div></div><div><h3>Methods</h3><div>Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the <em>Bio-Plex® Multiplex Immunoassay</em>. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).</div></div><div><h3>Results</h3><div>Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks <em>vs</em> 39 + 4 weeks, <em>p</em> = 0.005) and had smaller babies (2940 g, 30.0 centile <em>vs</em> 3415 g, 63.5 centile, <em>p</em> &lt; 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GRO<em>α</em> increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, <em>p</em> &lt; 0.001; third trimester, <em>p</em> = 0.045). Women in the CHD-group had higher levels if IL-6 (<em>p</em> = 0.005) and ICAM (p &lt; 0.001) lower levels of IL-10 in the third trimester (<em>p</em> = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (r_s = 1.00, <em>p</em> &lt; 0.001) in the CHD group.</div></div><div><h3>Conclusion</h3><div>There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GRO<em>α</em> and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156886"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling NLR pathway signatures: EP300 and CPN60 markers integrated with clinical data and machine learning for precision NASH diagnosis","authors":"Marwa Matboli ,&nbsp;Noha E. El-Attar ,&nbsp;Ibrahim Abdelbaky ,&nbsp;Radwa Khaled ,&nbsp;Maha Saad ,&nbsp;Amani Mohamed Abdel Ghani ,&nbsp;Eman Barakat ,&nbsp;Reginia Nabil Mikhail Guirguis ,&nbsp;Eman Khairy ,&nbsp;Shaimaa Hamady","doi":"10.1016/j.cyto.2025.156882","DOIUrl":"10.1016/j.cyto.2025.156882","url":null,"abstract":"<div><h3>Background</h3><div>Given the increasing prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH), there is a critical need for accurate non-invasive early diagnostic markers.</div></div><div><h3>Objective</h3><div>This study aimed to validate NLRP3-related RNA signatures (EP300, CPN60, and ITGB1 mRNAs, miR-6881-5p, and LncRNA-RABGAP1L-DT-206) using an integrated molecular approach and advanced machine-learning algorithms to identify robust biomarkers for early diagnosis of NASH.</div></div><div><h3>Methods</h3><div>A cohort of 237 participants (117 Healthy controls, 60 MAFLD, 120 NASH) was utilized. Twenty-five demographic, clinical, and molecular features were collected from each participant. Various machine learning models were trained on the dataset.</div></div><div><h3>Results</h3><div>The Random Forest algorithm emerged as the most effective classifier. The model identified nine key features: EP300 mRNA, CPN60 mRNA, AST, D. bilirubin, Albumin, GGT, HbA1c, HOMA-IR, and BMI, achieving an impressive 97 % accuracy in distinguishing NASH from non-NASH cases.</div></div><div><h3>Conclusion</h3><div>The integration of molecular, clinical, and demographic data with machine learning algorithms provides a highly accurate method for the early diagnosis of NASH. This model holds promise for early detection in individuals at risk of progressing to cirrhosis or liver cancer and may aid in identifying new therapeutic targets for managing NASH.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156882"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350707","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":"Different IL-1β levels differentially mediate neuroprotection or neurodegeneration and may be related to BDNF","authors":"Sifan Long ,&nbsp;Yanmei Wang ,&nbsp;Rong Cheng ,&nbsp;Liuyuan Deng ,&nbsp;Lixing Chen ,&nbsp;Yilong Dong","doi":"10.1016/j.cyto.2025.156877","DOIUrl":"10.1016/j.cyto.2025.156877","url":null,"abstract":"<div><h3>Background</h3><div>The detrimental and protective effects of interleukin 1β (IL-1β) have been reported. We have previously shown that the periods of IL-1β elevation is related to its dual effects. However, the effects of different IL-1β concentrations on neuropathological processes are unclear. Studies have demonstrated that mature brain-derived neurotrophic factor (mBDNF) and its precursor (proBDNF) have opposing functions in neuronal survival. We previously showed that mBDNF is involved in IL-1β-mediated neuropathology. Here, we investigated whether different IL-1β concentrations differentially affect mBDNF and proBDNF, determining their beneficial or harmful effects.</div></div><div><h3>Methods</h3><div>HT22 cells were cultured and exposed to various IL-1β concentrations for different durations. HT22 cell viability and the expression of mBDNF, proBDNF and their receptors were evaluated by a Cell Counting Kit-8 (CCK-8) assay and western blot.</div></div><div><h3>Results</h3><div>Compared with untreated cells, a significant reduction in cell viability was observed after exposure to high IL-1β concentrations for more than 24 h. Increased expression of proBDNF and its receptor p75NTR and decreased expression of mBDNF and its receptor TrkB, as well as decreased furin and PC1/3 (which promote the cleavage of proBDNF to mBDNF) expression, were detected. In contrast, low IL-1β concentrations increased cell viability, but a significant effect was observed only at an optimal concentration; in contrast to our predictions, low IL-1β concentrations did not induce significant alterations in mBDNF and proBDNF expression levels, but rather, low concentrations significantly increased the mBDNF/proBDNF ratio.</div></div><div><h3>Conclusions</h3><div>These results demonstrated that changes induced by low (neuroprotection) and high (neurodegeneration) IL-1β concentrations were oriented in different directions. These dual effects occur partly through the modulation of mBDNF signaling.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156877"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350706","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":"Are F2-isoprostanes a better marker of semen lipid peroxidation than MDA in reproductive pathologies with inflammatory basis?","authors":"Elena Moretti ,&nbsp;Cinzia Signorini ,&nbsp;Silvia Menchiari ,&nbsp;Laura Liguori ,&nbsp;Roberta Corsaro ,&nbsp;Laura Gambera ,&nbsp;Giulia Collodel","doi":"10.1016/j.cyto.2025.156889","DOIUrl":"10.1016/j.cyto.2025.156889","url":null,"abstract":"<div><div>Many male reproductive pathologies and a part of undiagnosed infertility share an oxidative stress (OS) etiology with high reactive oxygen species and cytokine concentrations. The lack of reliable biomarkers to quantify oxidative injury is a crucial problem in the field of male infertility. In this observational study, IL-1β and the OS markers malondialdehyde (MDA) and F₂-isoprostanes (F₂-IsoPs) were quantified in seminal plasma of 46 infertile patients with varicocele, genitourinary infections, idiopathic infertility, and 11 fertile men. Semen analysis was performed following WHO guidelines, IL-1β was determined by ELISA, MDA was quantified by HPLC, and F₂-IsoPs by GC/NICI-MS analysis. F₂-IsoPs were immunolocalized in spermatozoa of fertile and infertile subjects. Results indicated that F₂-IsoP, MDA, and IL-1β seminal levels positively correlated pairwise (<em>p</em> &lt; 0.001) and showed negative correlations with sperm parameters (p &lt; 0.001). Then, the studied population was grouped following the cause of infertility and the variables were compared between the different groups and a control sample. Seminal IL-1β, F₂-IsoPs, and MDA were significantly higher in varicocele (<em>p</em> &lt; 0.001, for MDA <em>p</em> &lt; 0.01) and genitourinary infections (p &lt; 0.001, for IL-1β p &lt; 0.01) groups than those observed in fertile subjects. F₂-IsoPs seemed to discriminate more accurately than MDA the different conditions, in particular idiopathic infertility. ROC curves demonstrated that the three analyzed indices were able to discriminate fertile and infertile patients. The immunofluorescence studies showed a low presence of F₂-IsoPs in spermatozoa of fertile men and an evident labeling in the tail, and cytoplasmic residues of spermatozoa from infertile patients. In conclusion, this data confirmed that F₂-IsoP level is a suitable marker of OS in seminal plasma, even more accurate than MDA and can be proposed for measuring OS in the clinical setting.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156889"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372681","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":"Preparation and functional identification of various porcine cytokines","authors":"Shanshan Yang ,&nbsp;Qiuxia Cao ,&nbsp;Kexin Yan ,&nbsp;Chuanhong Wang ,&nbsp;Xu Song ,&nbsp;Xianyu Bian ,&nbsp;Sufen Li ,&nbsp;Zhenkong Cheng ,&nbsp;Xuehan Zhang ,&nbsp;Yi Wang ,&nbsp;Rongli Guo ,&nbsp;Xiaodu Wang ,&nbsp;Houhui Song ,&nbsp;Baochao Fan ,&nbsp;Bin Li","doi":"10.1016/j.cyto.2025.156880","DOIUrl":"10.1016/j.cyto.2025.156880","url":null,"abstract":"<div><div>The insufficiency of current Porcine Epidemic Diarrhea (PED) vaccines against highly pathogenic strains highlights the critical importance of enhancing mucosal immunity in the prevention and control of porcine enteric viral diseases. Due to limited research platforms, the understanding of the porcine mucosal immune system and its response mechanisms remains incomplete. This study employed prokaryotic expression and purification methods to obtain eight essential cytokines involved in mucosal immune responses (CD40L, IL-2, IL-6, TNF-α, IL-13, IL-17α, TGF-β, APRIL). By utilizing various cell models including porcine intestinal organoids, IPEC-J2, Vero-E6, porcine peripheral blood lymphocytes, and porcine Peyer's patch lymphocytes, the functions of these eight cytokines were identified through flow cytometry, immunoblotting, relative quantitative PCR, and CFSE proliferation assays. The results demonstrate that all eight purified proteins exhibit both protein activity and function. The purification of these molecules lays the groundwork for further exploration of the mucosal barrier of pigs and mucosal immune-related studies, as well as providing research tools for the prevention and control of enteric viral diseases in pigs.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156880"},"PeriodicalIF":3.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143343577","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":"IL-27 aggravates acute hepatic injury by promoting macrophage M1 polarization to induce Caspase-11 mediated Pyroptosis in vitro and in vivo","authors":"Lin Ye ,&nbsp;Liuyang Wang ,&nbsp;Gang Kuang ,&nbsp;Zhijiao Zhang ,&nbsp;Qiaozhi Peng ,&nbsp;Miao He ,&nbsp;Jing Fan","doi":"10.1016/j.cyto.2025.156881","DOIUrl":"10.1016/j.cyto.2025.156881","url":null,"abstract":"<div><h3>Objectives</h3><div>Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism.</div></div><div><h3>Materials and methods</h3><div>Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R^−/−) mice alongside RAW264.7 cells. Our study established an SP-associated AHI model through the intraperitoneal injections of lipopolysaccharide (LPS) + D-galactosamine (D-G). For examining the IL-27 impact on AHI, mice serum and liver tissue samples were gathered. Inflammatory factor levels in the liver and serum were detected using ELISA and immunohistochemistry. Immunofluorescence and Western blot techniques were employed for the detection of protein expression associated with polarization and pyroptosis in the liver, including iNOS, ARG-1, caspase-11, RAGE, and GSDMD. To further verify the IL-27 effects on macrophage polarization and pyroptosis and explore possible mechanisms involved, we used LPS-triggered RAW264.7 macrophages to assess AMPK/SIRT1 expression after IL-27 intervention. This study utilized Compound C (CC) to block the AMPK/SIRT1 pathway. The inflammatory response level and protein expression related to macrophage polarization and pyroptosis were measured again to reveal IL-27 implication in AHI and determine whether its role is associated with the AMPK/SIRT1 pathway.</div></div><div><h3>Results</h3><div>The results revealed that IL-27 exacerbated systemic inflammation and liver damage in AHI mice by promoting M1 macrophage polarization, thereby increasing pro-inflammatory phenotype macrophages (M1). This further exacerbated the inflammatory response and pyroptosis <em>in vivo</em> and <em>in vitro</em>. Additionally, IL-27 down-regulated p-AMPK and SIRT1 protein expression while overexpressing macrophage inflammatory mediators including IL-1β/6 and TNFα. Furthermore, IL-27 promoted increased RAGE and caspase-11 protein expression, aggravating macrophage pyroptosis. Employing CC to block the AMPK pathway further aggravated M1 macrophage polarization and pyroptosis <em>in vitro</em> and <em>in vivo</em>, ultimately worsening liver injury.</div></div><div><h3>Conclusions</h3><div>Here, IL-27 aggravates AHI by promoting macrophage M1 polarization to induce caspase-11-mediated pyroptosis <em>in vitro</em> and <em>in vivo</em>, which may be linked to the AMPK/SIRT1 signaling pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156881"},"PeriodicalIF":3.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143343574","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":"IL-17A, IL-23R, FCGR3A are associated with neuropsychiatric systemic lupus erythematosus susceptibility in pediatric patients with lupus nephritis","authors":"Chen Ye ,&nbsp;Lizhi Chen ,&nbsp;Lu Zhang ,&nbsp;Yifan Zheng ,&nbsp;Xiaohong Liu ,&nbsp;Zhijun Huang ,&nbsp;Kejing Tang ,&nbsp;Xiaoyun Jiang ,&nbsp;Pan Chen","doi":"10.1016/j.cyto.2025.156874","DOIUrl":"10.1016/j.cyto.2025.156874","url":null,"abstract":"<div><h3>Objective</h3><div>To comprehensively investigate the impact of candidate loci on the susceptibility to neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort of Chinese children with lupus nephritis (LN).</div></div><div><h3>Methods</h3><div>This case-control study included sixty-two patients. And the case group consisted of 12 LN patients appearing NPSLE, while the control group consisted of 50 LN patients. A total of fifty-four single nucleotide polymorphisms (SNPs) across twenty genes were genotyped using the Agena Bioscience MassArray iPLEX platform. The associations between susceptibility to NPSLE and candidate SNPs were assessed using SNPStats online software. We evaluated the influence of candidate SNPs on the risk of NPSLE through odds ratios (OR) and 95 % confidence intervals (CI). Additionally, linkage disequilibrium (LD) and coefficient (D′ and r²) for haplotypes and their frequencies were performed using the genetic statistical online software SHEsis.</div></div><div><h3>Results</h3><div>Three significant SNPs were identified: <em>IL17RA</em> rs2895332, <em>IL23R</em> rs10889677, and <em>FCGR3A</em> rs396991. <em>AA</em> genotype of <em>FCGR3A</em> rs396991, GG genotype of <em>IL17RA</em> rs2895332 and AA genotype of <em>IL23R</em> rs10889677 exhibited a decreased risk of NPSLE compared to CA and CC genotypes, GA and AA genotypes, and CA and CC genotypes (rs396991 AA vs. CA-CC, OR 5.00, 95 %CI 0.99–25.17, <em>P</em> = 0.029; rs2895332 GG vs. GA-AA, OR 7.83, 95 %CI 1.47–41.79, <em>P</em> = 0.017; rs10889677 AA vs. CA-CC, OR 4.50, 95 %CI 1.08–18.69, <em>P</em> = 0.027). Furthermore, the haplotype A-T-G (<em>STAT4</em> rs13426947, rs1551443 and rs3024866) appeared to confer protection against the development of NPSLE. The multivariate logistic regression analysis indicated that two specific SNPs were significantly associated with an increased risk of NPSLE: [<em>FCGR3A</em> rs396991 (OR = 6.444, 95 %CI = 1.1–37.736, <em>P</em> = 0.039), <em>IL17RA</em> rs2895332 (OR = 0.128, 95 %CI = 0.017–0.963, <em>P</em> = 0.046)]. Notably, the RegulomeDB score of them reached 1 f. Using HaploReg, these loci were in strong LD (r²&gt;0.8) with several SNPs.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the polymorphisms <em>IL17RA</em> rs2895332, <em>IL23R</em> rs10889677, and <em>FCGR3A</em> rs396991 are significantly associated with the risk of NPSLE in childhood-onset LN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156874"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131156","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":"Kaempferol: Unveiling its anti-inflammatory properties for therapeutic innovation","authors":"Tatiana Elizabeth Sánchez Herrera ,&nbsp;Iván Patricio Salgado Tello ,&nbsp;Mohammed Ahmed Mustafa ,&nbsp;Nawfal Yousif Jamil ,&nbsp;Mohd Alaraj ,&nbsp;Kamil K. Atiyah Altameem ,&nbsp;Mohammed Qasim Alasheqi ,&nbsp;Abdul-Hameed M. Hamoody ,&nbsp;Adnan Taan Alkhafaji ,&nbsp;Maha Noori Shakir ,&nbsp;Mohammad Y. Alshahrani ,&nbsp;Ahmed Alawadi","doi":"10.1016/j.cyto.2024.156846","DOIUrl":"10.1016/j.cyto.2024.156846","url":null,"abstract":"<div><div>Inflammation, driven by various stimuli such as pathogens, cellular damage, or vascular injury, plays a central role in numerous acute and chronic conditions. Current treatments are being re-evaluated, prompting interest in naturally occurring compounds like kaempferol, a flavonoid prevalent in fruits and vegetables, for their anti-inflammatory properties. This study explores the therapeutic potential of kaempferol, focusing on its ability to modulate pro-inflammatory cytokines and its broader effects on inflammatory signaling pathways. Comprehensive reviews of in vitro and in vivo studies were conducted to elucidate the mechanisms underlying its anti-inflammatory and antioxidant actions. Kaempferol effectively inhibits the production of key inflammatory mediators, including cytokines and enzymes such as COX-2 and iNOS, while also targeting oxidative stress pathways like Nrf2 activation. The compound demonstrated protective effects in various inflammatory conditions, including sepsis, neurodegenerative disorders, cardiovascular diseases, and autoimmune conditions, by modulating pathways such as NF-κB, MAPK, and STAT. Despite its promise, kaempferol's clinical application faces challenges related to its bioavailability and stability, underscoring the need for advanced formulation strategies. These findings position kaempferol as a promising candidate for anti-inflammatory therapy, with the potential to improve patient outcomes across a wide range of inflammatory diseases. Further clinical studies are required to validate its efficacy, optimize dosage, and address pharmacokinetic limitations.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156846"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925930","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":"Role of TNFRSF12A in cell proliferation, apoptosis, and proinflammatory cytokine expression by regulating the MAPK and NF-κB pathways in thyroid cancer cells","authors":"Qiu Xu ,&nbsp;Gai Fan ,&nbsp;Su Shao","doi":"10.1016/j.cyto.2024.156841","DOIUrl":"10.1016/j.cyto.2024.156841","url":null,"abstract":"<div><div>Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) has been reported to be upregulated in thyroid cancer (THCA). However, the role and mechanism of TNFRSF12A in THCA remain largely unknown. TNFRSF12A expression in THCA samples was analyzed using bioinformatics analysis. CCK-8, EdU incorporation assay, TUNEL, and caspase-3 activity assay was used to detect cell proliferation and apoptosis in THCA cells. Correlated genes of TNFRSF12A were identified using LinkedOmics database and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Western blot analysis was performed to determine proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1), Bax, and Bcl-2 expression and to analyze the effect of TNFRSF12A on mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. Results showed that TNFRSF12A was increased in THCA tissue samples and cells. KEGG analysis showed that correlated genes of TNFRSF12A were significantly enriched in MAPK and NF-κB signaling pathways. Moreover, TNFRSF12A knockdown inactivated the MAPK and NF-κB signaling pathways in THCA cells. TNFRSF12A silencing alone or combined with inhibitor of ERK (PD98059), JNK (SP600125), p38 (SB203580), or NF-κB (Bay 11-7082) impeded cell proliferation and reduced PCNA and CCND1 expression in THCA cells. Meanwhile, TNFRSF12A knockdown alone or combined with PD98059, SP600125, SB203580, or Bay 11-7082 facilitated cell apoptosis, increased caspase-3 activity, downregulated Bcl-2 expression, and upregulated Bax expression in THCA cells. TNFRSF12A knockdown alone or combined with PD98059, SP600125, SB203580, or Bay 11–7082 also decreased the expression levels of proinflammatory cytokines IL-1β, IL-6, and IL-8 in THCA cells. On the contrary, TNFRSF12A overexpression showed an opposite effect. Treatment with PD98059, SP600125, SB203580, or Bay 11-7082 reversed the effects of TNFRSF12A overexpression on cell proliferation, apoptosis, and proinflammatory cytokine expression. In conclusion, the effects of TNFRSF12A on proliferation, apoptosis, and proinflammatory cytokine expression in THCA cells were regulated by the MAPK and NF-κB pathways.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156841"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884884","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":"Influence of head and neck cancer exosomes on macrophage polarization","authors":"Joni Yadav ,&nbsp;Tanya Tripathi ,&nbsp;Apoorva Chaudhary ,&nbsp;Divya Janjua ,&nbsp;Udit Joshi ,&nbsp;Nikita Aggarwal ,&nbsp;Arun Chhokar ,&nbsp;Chetkar Chandra Keshavam ,&nbsp;Anna Senrung ,&nbsp;Alok Chandra Bharti","doi":"10.1016/j.cyto.2024.156831","DOIUrl":"10.1016/j.cyto.2024.156831","url":null,"abstract":"<div><h3>Background</h3><div>Tumor cells within the tumor microenvironment (TME) release exosomes that influence macrophage phenotypes, either pro-tumorigenic or anti-tumorigenic. This mechanism, especially in head and neck squamous cell carcinoma (HNSCC), remains poorly understood. This study investigates the role of HNSCC exosomes in macrophage polarization.</div></div><div><h3>Methodology</h3><div>Exosomes were isolated from HPV16-positive (93VU147T, UDSCC2) and HPV-negative (OCT1) HNSCC cell lines. These exosomes were characterized for their potential to modulate macrophage polarization. Uptake of PKH-26 labeled exosomes by macrophages was monitored via confocal microscopy. Changes in macrophage polarization were assessed using quantitative real-time PCR and immunoblotting. Exosomal transcripts and proteome cargo was examined for polarization associated mediators.</div></div><div><h3>Results</h3><div>HPV-negative exosomes showed higher uptake by THP1 resting macrophages (M0). Exosomes from HPV-positive cells induced a mixed macrophage phenotype (M1 and M2), whereas HPV-negative exosomes favored M1 polarization. Immunoblotting analysis revealed that this polarization was driven by the activation of transcription factors STAT1, NF-κB, and AP1. Transcriptomic analysis of HNSCC exosomes revealed reads for AP1 (c-Jun, c-Fos, FosB, Fra1, Fra2) and NF-κB (p50/105, p52/100, RelA, RelB, c-Rel), along with their known upstream mediators MEK1‐–7, JNK1–3, JAK1–3, TYK2, IKKα, and IKKβ. Splice variants of macrophage polarization markers, including iNOS and TGFβ, were also identified, though none of the exosomal proteome component corresponded to these factors.</div></div><div><h3>Conclusion</h3><div>HPV-negative exosomes are efficiently internalized by macrophages, promoting M1 polarization likely via modulation of STAT1, NF-κB, and AP1 signaling. These findings provide novel insights into role of tumor exosomes in modulation of macrophage-mediated TME dynamics in HNSCC.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156831"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862592","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}