Immunobiology最新文献

{"title":"The involvement of oxidative stress and the TLR4/NF-κB/NLRP3 pathway in acute lung injury induced by high-altitude hypoxia","authors":"Wangjie Cao ,&nbsp;Yuanding Zeng ,&nbsp;Yun Su ,&nbsp;Hongxia Gong ,&nbsp;Jianzheng He ,&nbsp;Yongqi Liu ,&nbsp;Congyi Li","doi":"10.1016/j.imbio.2024.152809","DOIUrl":"10.1016/j.imbio.2024.152809","url":null,"abstract":"<div><h3>Objective</h3><p>This study investigated the effect of oxidative stress and the TLR4/NF-κB/NLRP3 pathway on the pathogenesis of acute lung injury (ALI) induced by high-altitude hypoxia.</p></div><div><h3>Methods</h3><p>Rats were placed in an animal hyperbaric oxygen chamber to establish a rat model of ALI induced by high-altitude hypoxia after treatment with N-acetylcysteine (NAC; a reactive oxygen species [ROS] inhibitor) or/and MCC950 (an NLPR3 inflammasome inhibitor). After modeling, the wet-to-dry weight ratio (W/D) of rat lung tissues was calculated. In lung tissues, ROS levels were detected with immunofluorescence, the enzyme activity was tested with the kit, and the expression of TLR4/NF-κB/NLRP3 pathway-related genes and proteins was measured with western blotting and qRT-PCR. The levels of inflammatory factors in the serum were quantified with ELISA.</p></div><div><h3>Results</h3><p>After modeling, rats showed significantly increased W/D, ROS levels, and Malondialdehyde (MDA) concentrations and markedly diminished Superoxide dismutase (SOD) and Glutathione (GSH) concentrations in lung tissues (all <em>P</em> &lt; 0.01), accompanied by substantially enhanced serum levels of TNF-α, IL-6, and IL-1β, significantly reduced serum levels of IL-10, and remarkably augmented TLR4, NLRP3, p-NF-κB p65, NF-κB p65 mRNA, and Caspase-1 expression in lung tissues (all <em>P</em> &lt; 0.01). Furthermore, treatment with NAC or MCC950 alone or in combination prominently lowered the W/D of lung tissues (<em>P</em> &lt; 0.01), serum levels of TNF-α (<em>P</em> &lt; 0.05), IL-6 (<em>P</em> &lt; 0.05), and IL-1β (<em>P</em> &lt; 0.01), and NF-κB p65 expression and phosphorylation (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) while significantly increasing SOD and GSH concentrations (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) and serum levels of IL-10 (<em>P</em> &lt; 0.01) in modeled rats. Meanwhile, treatment of NAC alone or combined with MCC950 significantly reduced MDA concentration and ROS levels (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01) in modeled rats, and treatment of MCC950 alone or combined with NAC considerably declined TLR4, NLRP3, and Caspase-1 expression in modeled rats (<em>P</em> &lt; 0.05, <em>P</em> &lt; 0.01).</p></div><div><h3>Conclusion</h3><p>Inhibition of oxidative stress and the TLR4/NF-κB/NLRP3 pathway can ameliorate ALI in rats exposed to high-altitude hypoxia.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152809"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000275/pdfft?md5=f25edf5c948cf75bef00c87105c842c3&pid=1-s2.0-S0171298524000275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141053838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antipyretic and anti-inflammatory effects of inosine, an active component of Kangfuxin","authors":"Yue Zhang ,&nbsp;Daqi Jia ,&nbsp;Yipeng Wu ,&nbsp;Yongqing Xu","doi":"10.1016/j.imbio.2024.152812","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152812","url":null,"abstract":"<div><p>Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152812"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000305/pdfft?md5=a0a9daf915cdcdab7fe546ec0fd73801&pid=1-s2.0-S0171298524000305-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD” [Immunobiology 217/3 (2012) 345–353]","authors":"Mirella Profita ,&nbsp;Loredana Riccobono ,&nbsp;Angela Marina Montalbano ,&nbsp;Anna Bonanno ,&nbsp;Maria Ferraro ,&nbsp;Giusy Daniela Albano ,&nbsp;Stefania Gerbino ,&nbsp;Paola Casarosa ,&nbsp;Michael Paul Pieper ,&nbsp;Mark Gjomarkaj","doi":"10.1016/j.imbio.2024.152800","DOIUrl":"10.1016/j.imbio.2024.152800","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152800"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000184/pdfft?md5=eb7474231d69bfc5afc258b8a5a9fff9&pid=1-s2.0-S0171298524000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage","authors":"Fangxiang Mu,&nbsp;Chen Wang,&nbsp;Lin Liu,&nbsp;Xianghui Zeng,&nbsp;Fang Wang","doi":"10.1016/j.imbio.2024.152808","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152808","url":null,"abstract":"<div><h3>Objectives</h3><p>Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM.</p></div><div><h3>Methods</h3><p>This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events.</p></div><div><h3>Results</h3><p>In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127–5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170–0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041–6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039–8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539–11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications.</p></div><div><h3>Conclusions</h3><p>TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152808"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000263/pdfft?md5=47fe2a4a545794de69cd120b3ac46139&pid=1-s2.0-S0171298524000263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The heterogeneity of tumour-associated macrophages contributes to the clinical outcomes and indications for immune checkpoint blockade in colorectal cancer patients","authors":"Junhui Tang ,&nbsp;Liang Ming ,&nbsp;Feiyu Qin ,&nbsp;Yan Qin ,&nbsp;Duo Wang ,&nbsp;Liuying Huang ,&nbsp;Yulin Cao ,&nbsp;Zhaohui Huang ,&nbsp;Yuan Yin","doi":"10.1016/j.imbio.2024.152805","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152805","url":null,"abstract":"<div><p>Tumor-associated macrophages (TAMs), one of the major immune cell types in colorectal cancer (CRC) tumor microenvironment (TME), play indispensable roles in immune responses against tumor progression. In this study, we aimed to know whether the extensive inter and intra heterogeneity of TAMs contributes to the clinical outcomes and indications for immune checkpoint blockade (ICB) in CRC. We used single-cell RNA sequencing (scRNA-Seq) data from 60 CRC patients and charactrized TAMs based on anatomic locations, tumor regions, stages, grades, metastatic status, MSS/MSI classification and pseudotemporal differentiation status. We then defined a catalog of 21 gene modules that determine macrophage status, and identified 7 of them as relevant to clinical outcomes and 11 as indications for ICB therapy. On this basis, we constructed a unique TAM subgroup profile, aiming to find features that may be highly responsive to immunotherapy for the CRC with poor prognosis under conventional treatment. This TAM subpopulation is enriched in tumors and is associated with poor prognosis, but exhibits a high immunotherapy response signature (HIM TAM). Further spatial transcriptome analysis and ligand-receptor interaction analysis confirmed that HIM TAM is involved in shaping TIME, especially the regulation of T cells. Our study provides insights into different TAM subtypes, highlights the importance of TAM heterogeneity in relation to patient prognosis and immunotherapy response, and reveals potential immunotherapy strategies based on TAM characteristics for CRC that does not respond well to conventional therapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152805"},"PeriodicalIF":2.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000238/pdfft?md5=685e3685df77a838f356fef60a790483&pid=1-s2.0-S0171298524000238-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia","authors":"Shiyi Pan ,&nbsp;Qinghua Cai ,&nbsp;Yiqiong Wei ,&nbsp;Tang Haifeng ,&nbsp;Yuping Zhang ,&nbsp;Wei Zhou ,&nbsp;Tingfen Deng ,&nbsp;Wenjian Mo ,&nbsp;Shunqing Wang ,&nbsp;Caixia Wang ,&nbsp;Cunte Chen","doi":"10.1016/j.imbio.2024.152804","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152804","url":null,"abstract":"<div><h3>Background</h3><p>Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known.</p></div><div><h3>Methods</h3><p>The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation.</p></div><div><h3>Results</h3><p>In both GZFPH and TCGA cohorts, high expression of ICOS was significantly associated with poor overall survival (OS) in patients with AML (<em>P</em> &lt; 0.05). Importantly, co-expression of ICOS and PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 predicted poor OS in AML; among them, ICOS/PD-1 was the optimal combination of immune checkpoints (ICs). The co-expression of ICOS and PD-1 was correlated with poor OS in non-acute promyelocytic leukemia (non-APL) patients following chemotherapy. Additionally, ICOS/PD-1 was an independent OS-predicting factor (<em>P</em> &lt; 0.05). Notably, a nomogram model was constructed by combining ICOS/PD-1, age, European Leukemia Net (ELN) risk stratification, and therapy to visually and personalized predict the 1-, 3-, and 5-year OS of patients with non-APL.</p></div><div><h3>Conclusion</h3><p>Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152804"},"PeriodicalIF":2.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000226/pdfft?md5=a41818c33f867a0053765c2149deef06&pid=1-s2.0-S0171298524000226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in the immune landscape characterized by inflammatory activation and immune escape within 12 h after trauma","authors":"Chenghu Song ,&nbsp;Weici Liu ,&nbsp;Yu Luo ,&nbsp;Jiwei Liu ,&nbsp;Guanyu Jiang ,&nbsp;Ruixin Wang ,&nbsp;Zhao He ,&nbsp;Xiaokun Wang ,&nbsp;Wenjun Mao","doi":"10.1016/j.imbio.2024.152801","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152801","url":null,"abstract":"<div><h3>Background</h3><p>Trauma is statistically a significant cause of mortality among patients across countries. Nevertheless, the precise correlation between genetic diagnostic markers and the intricate mechanism of trauma remains indistinct.</p></div><div><h3>Methods</h3><p>Our study exclusively centered on trauma patients and selected three trauma-related datasets from the Gene Expression Omnibus (GEO) database, all of which had blood samples collected within post-traumatic 12 h. Differential gene screening, the WGCNA and Cytoscape software were employed to analyze the two datasets, with a particular emphasis on the top 100 genes selected based on MCC algorithm scores. A logistic diagnostic model was constructed by analyzing the intersection genes in the third dataset, leading to the identification of diagnostic biomarkers with high efficiency. The global immune landscape of these patients was extensively investigated using a multidimensional approach. Meanwhile, the underlying pathological and physiological mechanisms associated with early trauma status are summarized by integrating existing literature.</p></div><div><h3>Results</h3><p>Out of these two GEO datasets, 21 overlapping genes were identified and incorporated into in the logistic diagnostic model constructed in the GSE36809 dataset. A panel of 9 genes was uncovered as a diagnostic biomarker, and their expression and correlation were subsequently verified. Additionally, by virtue of various algorithms, the findings revealed an upregulation of neutrophil expression and a downregulation of CD8+ T cell expression, indicating characteristic early trauma-induced inflammation activation and immune suppression. The correlation observed between the feature genes and immune cells serves to validate the exceptional diagnostic capability of these 9 genes in identifying trauma status and their promising potential for patients who could benefit from targeted immune interventions. Drawing from these findings, the discussion section offers insights into the underlying pathological and physiological mechanisms at play.</p></div><div><h3>Conclusion</h3><p>Our research has discovered a novel diagnostic biomarker and unveiled its association with post-traumatic immune alterations. This breakthrough enables accurate and timely diagnosis of early trauma, facilitating the implementation of appropriate healthcare interventions.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152801"},"PeriodicalIF":2.8,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000196/pdfft?md5=b31ee75ff4ec81e8d6eeea3663a806c7&pid=1-s2.0-S0171298524000196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA SNHG1 overexpression alleviates osteoarthritis via activating PI3K/Akt signal pathway and suppressing autophagy","authors":"Qiushi Wang,&nbsp;Jie Yang,&nbsp;Rui Pan,&nbsp;Zhengang Zha","doi":"10.1016/j.imbio.2024.152799","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152799","url":null,"abstract":"<div><p>We hereby intend to further explore and confirm the underlying mechanism of Small nucleolar RNA Host Gene 1 (SNHG1) in osteoarthritis (OA). For <em>in vitro</em> assays, OA was induced in primary chondrocytes with interleukin-1β (IL-1β) treatment; while for <em>in vivo</em> tests, OA model was established in mice using the destabilization of the medial meniscus (DMM) method. Cell viability and apoptosis were assessed with MTT and flow cytometry assays, respectively. Cartilage tissue was stained by Safranin-O/Fast Green Staining. The mRNA and protein levels were separately determined via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. SNHG1 overexpression promoted the viability yet inhibited the apoptosis of chondrocytes injured by IL-1β. Moreover, the overexpression of SNHG1 promoted B-cell lymphoma-2 (Bcl-2) expression and activated phosphoinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway but suppressed the process of autophagy, which led to down-regulation of light chain 3 (LC3)-II/I level and up-regulation of P62 level. However, rapamycin (RAPA, an autophagy activator) and LY294002 (a PI3K inhibitor) reversed the effects of SNHG1 overexpression on the viability and apoptosis of chondrocytes as well as on the proteins related to PI3K/Akt pathway and autophagy. In OA-modeled mice, SNHG1 overexpression prevented the loss of chondrocytes via the activation of PI3K/Akt pathway and the suppression of autophagy. SNHG1 overexpression might inhibit the apoptosis of chondrocytes by promoting PI3K/Akt pathway and inhibiting autophagy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152799"},"PeriodicalIF":2.8,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000172/pdfft?md5=71ea02c29534e067f3233b8b4ef54361&pid=1-s2.0-S0171298524000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of neutrophil extracellular trap levels with Raynaud’s phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil","authors":"Eduardo Delabio Auer ,&nbsp;Valéria Bumiller-Bini Hoch ,&nbsp;Emiliano Borges da Silva ,&nbsp;Yohan Ricci Zonta ,&nbsp;Luciane Alarcão Dias-Melicio ,&nbsp;Thelma Larocca Skare ,&nbsp;Vanessa F. Picceli ,&nbsp;Iara José Messias-Reason ,&nbsp;Angelica Beate Winter Boldt","doi":"10.1016/j.imbio.2024.152803","DOIUrl":"10.1016/j.imbio.2024.152803","url":null,"abstract":"<div><p>Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients’ cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into “High serum NET levels” and “Low serum NET levels” groups. All analyses were performed in R language 4.1.2, and <em>p</em> &lt; 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and <em>p</em> = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, <em>p</em> = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, <em>p</em> = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, <em>p</em> = 6 × 10⁻³). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152803"},"PeriodicalIF":2.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000214/pdfft?md5=2e87b717ec774929921c1e0a21e8600c&pid=1-s2.0-S0171298524000214-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway","authors":"Yizheng Wang ,&nbsp;Shiyang Zhang ,&nbsp;Zijun Zhao ,&nbsp;Qianxu Jin ,&nbsp;Zairan Wang ,&nbsp;Zihan Song ,&nbsp;Liqiang Liu ,&nbsp;Zongmao Zhao","doi":"10.1016/j.imbio.2024.152802","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152802","url":null,"abstract":"<div><h3>Background</h3><p>Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated.</p></div><div><h3>Methods</h3><p>This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored.</p></div><div><h3>Results</h3><p>Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway.</p></div><div><h3>Conclusions</h3><p>PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152802"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000202/pdfft?md5=2a1cf96018cd94641396b034b544da06&pid=1-s2.0-S0171298524000202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140342312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}