Marianno Franzini, Francesco Vaiano, Umberto Tirelli, Salvatore Chirumbolo, Luigi Valdenassi
{"title":"SIOOT recommendations for the optimal application of the oxygen-ozone therapy in clinical medicine.","authors":"Marianno Franzini, Francesco Vaiano, Umberto Tirelli, Salvatore Chirumbolo, Luigi Valdenassi","doi":"10.1016/j.intimp.2024.113751","DOIUrl":"10.1016/j.intimp.2024.113751","url":null,"abstract":"<p><p>Oxygen-ozone therapy has garnered increasing attention for its potential therapeutic applications, yet its widespread adoption is hindered by inconsistent protocols and a lack of standardized guidelines. Standardizing these protocols is essential to ensure the safety, efficacy, and reproducibility of treatments. Advanced training for physicians and caregivers is paramount, equipping them with evidence-based knowledge and practical expertise to administer this therapy effectively while avoiding unverified or misleading innovative approaches. Scientific Societies play a pivotal role in this endeavour, providing a structured framework for research, education, and dissemination of validated practices, thereby safeguarding patient welfare and fostering the responsible evolution of the field.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113751"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soheil Aminizadeh, Amir Hossein Moslemizadeh, Sara Sheibani, Zahra Sedighi-Khovidak, Zahrasadat Roholamini, Saeideh Jafarinejad-Farsangi, Reza Kheirandish, Vahid Sheibani, Hamideh Bashiri
{"title":"Preventive effect of MitoQ supplementation and endurance training on glioblastoma and its consequences: TLR4/CREB/ NF-κβ /IL-1β pathway and behaviors.","authors":"Soheil Aminizadeh, Amir Hossein Moslemizadeh, Sara Sheibani, Zahra Sedighi-Khovidak, Zahrasadat Roholamini, Saeideh Jafarinejad-Farsangi, Reza Kheirandish, Vahid Sheibani, Hamideh Bashiri","doi":"10.1016/j.intimp.2024.113756","DOIUrl":"10.1016/j.intimp.2024.113756","url":null,"abstract":"<p><strong>Objective: </strong>The present study investigated the preventive effect of MitoQ supplementation and endurance training (ET) on the TLR4/CREB/ NF-κβ signaling pathway, antioxidant indices, and behaviors in C6-induced glioblastoma (GBM) in rats.</p><p><strong>Methods: </strong>60 male Wistar rats were randomly divided into five groups (n = 12); Sham, Tumor, MitoQ, ET, and MitoQ + ET. Rats in the training groups performed endurance training (5 days per week), and MitoQ at the dose of 250 µM/L daily was administered in drinking water for 8 weeks. At the end of the protocol, all groups except the sham group received 1*10<sup>6</sup> tumor cells /10 µl culture medium. Two weeks after tumor induction, behavioral tests were performed, and then brain tissue was collected for the histopathology, measurement of antioxidant and inflammatory factors, TLR4, NF-κB proteins, and TLR4, NF-κβ, CREB, IL-1ß, TNF-a, IL-10, Bax, Bcl-2, and Caspase-3 gene expression.</p><p><strong>Results: </strong>The increased level of TLR4 and NF-κβ protein expression in GBM rats decreased in the treatment groups. Gene expression of TLR4, NF-κβ, CREB, TNF-a, IL-10, and Bcl-2 increased in the tumor groups, and treatment groups decreased TLR4, NF-κB, Bcl-2, and CREB. In addition, social behaviors, balance, and memory were impaired in the tumor group, which combination group could improve these behaviors.</p><p><strong>Conclusion: </strong>In sum, the preventive effects of MitoQ as a beneficial immune reactive agent and exercise training in rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, inflammatory factors, and down-regulation of the expression of TLR4.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113756"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Atractylenolide-III restrains cardiac fibrosis after myocardial infarction via suppression of the RhoA/ROCK1 and ERK1/2 pathway.","authors":"Xuelian Li, Xianjie Zhu, Shijiu Jiang, Wenling Yang, Fan Zhang, Xiaopeng Guo, Yumiao Wei","doi":"10.1016/j.intimp.2024.113825","DOIUrl":"10.1016/j.intimp.2024.113825","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibrosis, a critical factor in myocardial remodeling post-myocardial infarction (MI), can advance heart failure progression. Atractylenolide III (ATL-III), derived from Atractylodes lancea, has recognized antioxidant and anti-inflammatory effects; however, its influence on cardiac fibrosis remains unclear.</p><p><strong>Methods: </strong>MI was induced in mice by permanent ligation of the left anterior descending (LAD) coronary artery, followed by 2 weeks of ATL-III or dimethyl sulfoxide (DMSO) treatment. Cardiac fibrosis was assessed by echocardiography, tissue histology, and serum biomarkers of myocardial injury. In vitro, the effects of ATL-III on cardiac fibroblast (CF) proliferation and collagen deposition were evaluated using immunofluorescence, 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques. Network pharmacology and molecular docking identified potential ATL-III targets.</p><p><strong>Results: </strong>ATL-III treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) and fractional shortening (FS) and reduced left ventricular dilation. Histological analysis revealed decreased fibrotic areas in ATL-III-treated mice, along with reduced expression of fibrosis markers α-SMA and Collagen I. ATL-III also alleviated oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing superoxide dismutase (SOD) activity. Furthermore, ATL-III suppressed inflammation, decreasing TNF-α, IL-6, and IL-1β protein and mRNA levels. In vitro, ATL-III inhibited TGF-β1-induced CF proliferation, migration, and differentiation, reducing the expression of fibrotic markers. Mechanistically, ATL-III suppressed the RhoA/ROCK1 and ERK1/2 signaling pathways, as confirmed by molecular docking and pathway analysis.</p><p><strong>Conclusion: </strong>ATL-III demonstrates therapeutic potential in mitigating post-MI cardiac fibrosis by reducing oxidative stress, inflammation, and CF activation. These findings highlight ATL-III as a promising candidate for the treatment of cardiac fibrosis and associated heart failure.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113825"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Wang, Yao Chen, Jin Zhang, Ning Wang, Tian Tian
{"title":"Deletion of BRCC3 ameliorates airway inflammation in asthma by inhibiting the activation of NLRP3 inflammasome.","authors":"Hao Wang, Yao Chen, Jin Zhang, Ning Wang, Tian Tian","doi":"10.1016/j.intimp.2024.113720","DOIUrl":"10.1016/j.intimp.2024.113720","url":null,"abstract":"<p><p>BRCA1/BRCA2-containing complex subunit 3 (BRCC3) serves as a deubiquitinating enzyme contributing to multiple inflammation-related disorders. However, the role of BRCC3 in modulating airway inflammation in asthma has not been investigated. This study aimed to examine the role of BRCC3 in airway inflammation using a mouse model of asthma induced by ovalbumin (OVA). BRCC3 levels were found to be elevated in mice with asthma. BRCC3 knockout (KO) mice demonstrated a notable improvement in pathological changes, accompanied by reduced levels of inflammatory cell infiltration and inflammatory cytokines, compared to wild-type (WT) mice following OVA challenge. The NLRP3 inflammasome was high activated in asthmatic mice, which was restrained by BRCC3 KO, as companied by a decrease in NLRP3, ASC, cleaved Caspase-1, cleaved Gasdermin D (GSDMD), IL-1β, and IL-18. In vitro studies demonstrated BRCC3 levels increased in airway epithelial cells in response to house dust mite (HDM) stimulation, depending on the dose and duration of exposure. Silencing BRCC3 in airway epithelial cells protected against HDM-induced cell injury and inflammation, along with inhibiting the NLRP3 inflammasome and pyroptosis. Conversely, the overexpression of BRCC3 in airway epithelial cells worsened DM-induced cell injury and inflammation while also enhancing the NLRP3 inflammasome and pyroptosis. Further investigations revealed that silencing BRCC3 increased the ubiquitination of NLRP3, whereas overexpressing BRCC3 decreased it. Pharmacological inhibition of the NLRP3 inflammasome diminished the effects of BRCC3 overexpression on the inflammation and pyroptosis induced by HDM in airway epithelial cells. Overall, these findings underscore the importance of BRCC3 in the pathogenesis of asthma. Deletion of BRCC3 alleviates airway inflammation in asthma by impeding the activation of the NLRP3 inflammasome, thus indicating that BRCC3 could serve as a potential target for asthma therapy.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113720"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Integrative analysis of single-cell RNA-seq, transcriptome and Mendelian randomization for the Identification and validation of NAD<sup>+</sup> Metabolism-Related biomarkers in ulcerative colitis.","authors":"Longxiang Zhang, Jian Li, Qiqi Zhang, Jianshu Gao, Keke Zhao, Yersen Asai, Ziying Hu, Hongliang Gao","doi":"10.1016/j.intimp.2024.113765","DOIUrl":"10.1016/j.intimp.2024.113765","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic and refractory inflammatory disease of the colon and rectum. This study utilized bioinformatics methods to explore the potential of Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) metabolism-related genes (NMRGs) as key genes in UC. Using the GSE87466 dataset, differentially expressed NMRGs were identified through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and NMRG scoring. These NMRGs were used as exposure factors, with UC as the outcome, to identify causal candidate genes through Mendelian randomization (MR) analysis. Key genes were further validated as biomarkers using machine learning and expression validation in external datasets (GSE75214, GSE224758). A nomogram based on the expression levels of these biomarkers was constructed to predict UC risk, and the biomarkers' expression was validated through real-time quantitative polymerase chain reaction (RT-qPCR). Subsequently, signaling pathway analysis, enrichment analysis, immune infiltration analysis, and drug prediction were conducted to comprehensively understand the biological roles of the key genes in the human body. Single-cell (GSE116222) and spatial transcriptomic analyses (GSE189184) revealed the expression patterns of these key genes in specific cell types. NCF2, IL1B, S100A8, and SLC26A2 were identified as biomarkers, with NCF2 and IL1B serving as protective factors and S100A8 and SLC26A2 as risk factors for UC. The nomogram based on these biomarkers demonstrated strong predictive value. Functional analysis revealed significant IL1B, NCF2, and S100A8 enrichment in pathways such as IL-4 and IL-13 signaling, while SLC26A2 was strongly associated with respiratory electron transport. Significant differences in immune cells, such as macrophages and neutrophils, were also observed. Single-cell analysis showed high expression of NCF2, IL1B, and S100A8 in monocytes, while SLC26A2 was primarily expressed in epithelial cells, intestinal epithelial cells, and mast cells. Overall, these findings reveal the roles of NMRGs, providing valuable insights into the diagnosis and treatment of UC patients.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113765"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haneen A Al-Mazroua, Ahmed Nadeem, Sabry M Attia, Saleh A Bakheet, Ajaz Ahmad, Mushtaq A Ansari, Khalid E Ibrahim, Hatun A Alomar, Mohammed M Almutairi, Norah K Algarzae, Mohamed A Mahmoud, Marwa H Hussein, Omer M Ahmed, Sheikh F Ahmad
{"title":"The PPAR-α selective agonist WY14643 improves lupus nephritis via the downregulation of the RORγT/STAT3 signaling pathway in MRL/lpr mice.","authors":"Haneen A Al-Mazroua, Ahmed Nadeem, Sabry M Attia, Saleh A Bakheet, Ajaz Ahmad, Mushtaq A Ansari, Khalid E Ibrahim, Hatun A Alomar, Mohammed M Almutairi, Norah K Algarzae, Mohamed A Mahmoud, Marwa H Hussein, Omer M Ahmed, Sheikh F Ahmad","doi":"10.1016/j.intimp.2024.113787","DOIUrl":"10.1016/j.intimp.2024.113787","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a classic autoimmune disorder that mostly affects young women and involves various organs, such as the skin, joints, central nervous system, and kidneys. WY14643, a selective agonist of peroxisome proliferator-activated receptor-α, has previously shown anti-inflammatory effects in various disease models. However, its effects on lupus nephritis are yet to be explored. Therefore, the efficacy of WY14643 on renal biomarkers and lupus nephritis was assessed in MRL/lpr mice. Flow cytometry was used to examinethe effects of WY14643 on the expression of IL-17A, STAT3, RORγT, IL-21, IL-21R, IL-22, and TNF-α in splenic CD4<sup>+</sup> T cells. We further investigated the impact of WY14643 on the mRNA expression of IL-17A, STAT3, RORγT, IL-21, IL-21R, IL-22, and TNF-α in kidney tissue via RT-PCR analysis. The administration of WY14643 effectively improved the symptoms of lupus nephritis in MRL/lpr mice. The administration of WY14643 decreased serum albumin, urine protein, serum creatinine, and blood urea nitrogen levels in MRL/lpr mice. WY14643 reduced the levels of inflammatory markers, including CD4<sup>+</sup>IL-17A<sup>+</sup>, CD4<sup>+</sup>STAT3<sup>+</sup>, CD4<sup>+</sup>RORγT<sup>+</sup>, CD4<sup>+</sup>IL-21<sup>+</sup>, CD4<sup>+</sup>IL-21R<sup>+</sup>, CD4<sup>+</sup>IL-22<sup>+</sup>, and CD4<sup>+</sup>TNF-α<sup>+</sup>, in the spleen cells of MRL/lpr mice. Additionally, we discovered that the administration of WY14643 resulted in the suppression of mRNA levels of IL-17A, STAT3, RORγT, IL-21, IL-22, and TNF-α. The current work shows that the suppression of inflammatory cells by WY14643 may effectively reduce autoimmune characteristics, such as renal inflammation, in lupus-prone MRL/lpr mice. Therefore, WY14643, being a specific PPAR-α agonist, shows significant potential as a novel therapeutic option for treatingnephritis associated with SLE, offering hope for future treatments in this challenging field.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113787"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junjie Li, Xiaojuan Mi, Zhilun Yang, Ziqi Feng, Yong Han, Ting Wang, Haowen Lv, Yanbo Liu, Kang Wu, Juan Liu
{"title":"Minocycline ameliorates cognitive impairment in rats with trigeminal neuralgia by regulating microglial polarization.","authors":"Junjie Li, Xiaojuan Mi, Zhilun Yang, Ziqi Feng, Yong Han, Ting Wang, Haowen Lv, Yanbo Liu, Kang Wu, Juan Liu","doi":"10.1016/j.intimp.2024.113786","DOIUrl":"10.1016/j.intimp.2024.113786","url":null,"abstract":"<p><p>Trigeminal neuralgia (TN)-related cognitive impairment is a common cause of decreased quality of life in patients and is closely associated with neuroinflammation. Although minocycline has demonstrated anti-inflammatory, analgesic, and neuroprotective functions, its role in treating TN-related cognitive impairment remains unreported. In this study, we used an in vivo TN model and an in vitro model of primary microglial neuroinflammation to investigate the potential effects of minocycline on cognitive function and microglial polarization in TN rats. Our results suggested that minocycline treatment attenuated cognitive deficits by alleviating hippocampal neuronal damage and enhancing synaptic plasticity in TN rats. Furthermore, both in vitro and in vivo assays demonstrated that minocycline polarized activated microglia to the M2 phenotype, leading to the reduction of pro-inflammatory factors, including tumor necrosis factor-α and interleukin-1, and an increase in the anti-inflammatory factors, such as interleukin-4 and interleukin-10, thereby attenuating neuroinflammation. Moreover, it was found that the TLR4/MyD88/NF-κB pathway was involved in the shift of microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2). In summary, minocycline likely mediated the process of microglia polarization partly via the TLR4/MyD88/NF-κB pathway, promoting neuronal survival and restoring synaptic plasticity, thereby improving TN-related cognitive impairment.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113786"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Honghui Long, Yunze Tai, Jiwen Fan, Xiaoqi Ou, Lin Yan, Yu Fan, Weihua Feng, Jie Chen, Yi Li
{"title":"Characteristics of peripheral lymphocyte subsets and antibodies in COVID-19-infected kidney transplantation recipients.","authors":"Honghui Long, Yunze Tai, Jiwen Fan, Xiaoqi Ou, Lin Yan, Yu Fan, Weihua Feng, Jie Chen, Yi Li","doi":"10.1016/j.intimp.2024.113755","DOIUrl":"10.1016/j.intimp.2024.113755","url":null,"abstract":"<p><strong>Background: </strong>Peripheral lymphocyte subsets play vital roles in various disease conditions. However, the roles of kidney transplant recipients (KTRs) with novel coronavirus pneumonia (COVID-19) are still unclear. In this research, we investigated the predictive value of peripheral blood lymphocyte subsets on the severity of KTRs with COVID-19 and the correlation between antibodies and lymphocyte levels.</p><p><strong>Methods: </strong>84 patients with kidney transplantation combined with COVID-19 admitted from December 2022 to February 2023 were included. On the basis of the severity of COVID-19, they were categorized into a mild (n = 49) and a severe group (n = 35). The logistic regression method was utilized to build the critical risk prediction model for KTRs complicated with COVID-19. The receiver operator characteristic curve (ROC), calibration plot and clinical decision curve analysis (DCA) were applied to assess the discrimination, calibration and clinical application value of this model. The Spearman correlation test was applied to examine the connection between antibodies and various immune indexes.</p><p><strong>Results: </strong>Except for the increase of CD4<sup>+</sup>HLA-DR<sup>+</sup> T cells, the number of CD3<sup>+</sup>, CD4<sup>+</sup>, and CD8<sup>+</sup> T cell subsets in severe was lower than that in mild (P < 0.05). IL-6 in severe was higher than mild (P < 0.05). After screening variables, we established a regression equation prediction model, logit (P) = 4.965+ (-0.038) × (CD3<sup>+</sup>/lymphocytes (%)) + 0.064× (CD4<sup>+</sup>HLA-DR<sup>+</sup>/ CD4<sup>+</sup> T cells (%)) + (-0.040) × (CD14<sup>+</sup>HLA-DR<sup>+</sup>/monocytes (%)). The area under the ROC curve (AUC) of the prediction model was 0.779 (95 % CI 0.679-0.879, P = 0.001). The cut-off value was 0.308, with a prediction sensitivity of 0.829 (95 % CI 0.657-0.928) and a specificity of 0.653 (95 % CI 0.503-0.779). Logistic regression analysis showed the increase in the percentage of CD4<sup>+</sup>HLA-DR<sup>+</sup> T cells among CD4<sup>+</sup> T cells was a risk factor for COVID-19 severity among kidney transplant recipients, while the increase in the percentage of CD3<sup>+</sup> T cells among lymphocytes and CD14<sup>+</sup>HLA-DR<sup>+</sup> monocytes among CD14<sup>+</sup> monocytes acted as protective factors. COVID-19 antibodies were negatively correlated with CD8<sup>+</sup>CD45RA<sup>+</sup>CD27<sup>-</sup> (Terminally Differentiated Effector Memory T Cells, TEMRA), CD8<sup>+</sup>CD28<sup>-</sup>, CD8<sup>+</sup>CD38<sup>+</sup> and CD4<sup>+</sup>CD38<sup>+</sup> T cells, while positively correlated with CD8<sup>+</sup>CD45RA<sup>-</sup>CD27<sup>-</sup> (Effector Memory T cells, T8EM), CD8<sup>+</sup>CD45RA<sup>-</sup>CD27<sup>+</sup> (Central Memory T cells, T8CM) and CD8<sup>+</sup>CD28<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>A predictive model was developed and validated for predicting the severe form of COVI","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113755"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juntao Zhuang, Ming Zhou, Hao Yu, Rui Zhou, Kexin Bai, Jiancheng Lv, Kai Li, Yidong Cheng, Haiwei Yang, Xiao Yang, Qiang Lu
{"title":"CircFAM64A(3) promoted bladder cancer proliferation and inhibited CD8 + T cell via sponging to miR-149-5p and activated IL-6/JAK/STAT pathway.","authors":"Juntao Zhuang, Ming Zhou, Hao Yu, Rui Zhou, Kexin Bai, Jiancheng Lv, Kai Li, Yidong Cheng, Haiwei Yang, Xiao Yang, Qiang Lu","doi":"10.1016/j.intimp.2024.113762","DOIUrl":"10.1016/j.intimp.2024.113762","url":null,"abstract":"<p><strong>Background: </strong>The significance of circular RNA in tumour biology is increasingly recognized. This study aims to explore the value of circFAM64A(3) in the proliferation and immune evasion of bladder cancer.</p><p><strong>Methods: </strong>Bioinformatics were used to identify the differentially expressed circular RNAs in bladder cancer. Proliferation assay, co-culture assay and flow cytometry assay confirmed the oncogenic and immune-evading characteristics of circFAM64A(3) in bladder cancer in vitro and in vivo. Further, mRNA sequencing, RNA pulldown, and RNA immunoprecipitation were used to confirm the downstream targets and pathways regulated by circFAM64A(3). CUT&TAG assay confirmed HIF-1α promoted the expression of circFAM64A(3) under hypoxic.</p><p><strong>Results: </strong>CircFAM64A(3) was significantly high expression in bladder cancer tissues and related with poor prognosis of bladder cancer patients. CircFAM64A(3) promoted bladder cancer cells proliferation and immune evasion in vitro and in vivo. Mechanistically, circFAM64A(3) acted as a sponge to miR-149-5p and reduced the binding of miR-149-5p to IL-6 3'-UTR. Then, IL-6 activated the JAK/STAT pathway and caused an increase of PD-L1. Under hypoxic environment, HIF-1α bound to the promoter of FAM64A and promoted circFAM64A(3) transcription.</p><p><strong>Conclusion: </strong>HIF-1α/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113762"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M M Szachniewicz, K E van Meijgaarden, E Kavrik, W Jiskoot, J A Bouwstra, M C Haks, A Geluk, T H M Ottenhoff
{"title":"Cationic pH-sensitive liposomes as tuberculosis subunit vaccine delivery systems: Effect of liposome composition on cellular innate immune responses.","authors":"M M Szachniewicz, K E van Meijgaarden, E Kavrik, W Jiskoot, J A Bouwstra, M C Haks, A Geluk, T H M Ottenhoff","doi":"10.1016/j.intimp.2024.113782","DOIUrl":"10.1016/j.intimp.2024.113782","url":null,"abstract":"<p><p>Tuberculosis (TB) is a major global health problem, and the development of effective and safe vaccines is urgently needed. CD8<sup>+</sup> T-cells play an important role alongside CD4<sup>+</sup> T-cells in the protective immune response against TB. pH-sensitive liposomes are hypothesized to boost CD8<sup>+</sup> T-cell responses by promoting class I presentation through a mechanism involving pH-dependent endosomal escape and the cytosolic transfer of antigens. The aim of the study was to explore the potential of pH-sensitive liposomes as a novel delivery system for a multi-stage protein subunit vaccine against TB in primary human cells. The liposomes were formulated with the fusion antigen Ag85b-ESAT6-Rv2034 (AER), which was previously shown to be effective in reducing bacterial load in the lungs HLA-DR3 transgenic mice and guinea pigs. The liposomes were assessed in vitro for cellular uptake, cell viability, upregulation of cell surface activation markers, induction of cytokine production using human monocyte-derived dendritic cells (MDDCs), and activation of human antigen-specific T-cells. Liposome DOPC:DOPE:DOBAQ:EPC (3:5:2:4 M ratio) was effectively taken up, induced several cell surface activation markers, and production of CCl3, CCL4, and TNFα in MDDCs. It also induced upregulation of CD154 and IFNγ in T-cell clones in an antigen-specific manner. Thus, cationic pH-sensitive liposome-based TB vaccines have been demonstrated to be capable of inducing robust protective Mtb-specific immune responses, positioning them as promising candidates for effectiveTBvaccination.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113782"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}