
自引率: 1%
被引量: 2829
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国人发稿量: 9
投稿须知/期刊简介:
Published by Nature Publishing Group. ISSN: 1466-4879.<br /><br />Genes and Immunity is dedicated to presenting functional immunogenetics, understanding how this new field controls the immune system to maintain health and defining its role in disease development, progression and severity. The journal provides a new forum for research in immunobiology, bringing together studies which focus on the role of genetic, genomic and functional diversity in determining normal and abnormal immunological function. Genes and Immunity emphasizes the emergence of functional immunogenetics and genomics and their role in understanding the immune system and the pathogenesis of immune-mediated diseases, including autoimmunity, infectious diseases, chronic inflammatory disorders and malignancy.
期刊描述简介:
Published by Nature Publishing Group. ISSN: 1466-4879. Genes and Immunity is dedicated to presenting functional immunogenetics, understanding how this new field controls the immune system to maintain health and defining its role in disease development, progression and severity. The journal provides a new forum for research in immunobiology, bringing together studies which focus on the role of genetic, genomic and functional diversity in determining normal and abnormal immunological function. Genes and Immunity emphasizes the emergence of functional immunogenetics and genomics and their role in understanding the immune system and the pathogenesis of immune-mediated diseases, including autoimmunity, infectious diseases, chronic inflammatory disorders and malignancy.
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LncRNA sequencing reveals an essential role for the lncRNA-mediated ceRNA network in penile squamous cell carcinoma.
Penile squamous cell carcinoma (PSCC) is becoming increasingly common and posing a severe threat to men's health, particularly in developing countries. The function of long non-coding RNAs (lncRNAs) in PSCC progression remains mysterious. Therefore, we explored the significance of lncRNAs in the competing endogenous RNA (ceRNA) network in PSCC tumor progression. The 5 healthy and 6 tumor tissue samples were subjected to lncRNA sequencing. Using miRcode, LncBase, miRTarBase, miRWalk, and TargetScan, we constructed a ceRNA network of differentially expressed lncRNAs, miRNAs, and mRNAs. Our analysis resulted in a ceRNA network consisting of 4 lncRNAs, 18 miRNAs, and 38 mRNAs, whose upstream regulators, the lncRNAs MIR205HG, MIAT, HCP5, and PVT1, were all elevated in PSCC. Immunohistochemical staining confirmed that cell proliferation-related genes TFAP2C, MKI67, and TP63, positively regulated by 4 lncRNAs, were considerably overexpressed in tumor tissues. Immune analysis revealed a significant upregulation in macrophage and exhausted T cell infiltration in PSCC. Our study identified a lncRNA-miRNA-mRNA ceRNA network for PSCC, revealing possible molecular mechanisms involved in the regulation of PSCC progression by key lncRNAs and their connections to the immunosuppressive tumor microenvironment. The ceRNA network provides a novel perspective for elucidating the pathogenesis of PSCC.
被引量:- 发表:1970
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Integrated machine learning survival framework to decipher diverse cell death patterns for predicting prognosis in lung adenocarcinoma.
Various forms of programmed cell death (PCD) collectively regulate the occurrence, development and metastasis of tumors. Nevertheless, a comprehensive analysis of the diverse types of PCD in lung adenocarcinoma (LUAD) is currently lacking. The study encompassed a total of 1481 genes associated with the regulation of 13 distinct PCD patterns. Ten machine learning algorithms were amalgamated into 101 combinations, from which the optimal algorithm was chosen to formulate an artificial intelligence-derived prognostic signature based on the average C-index across four multicenter cohorts. The established optimal cell death index (CDI) model emerged as an independent risk factor for overall survival, demonstrating robust and consistent performance. Notably, CDI exhibited significantly higher accuracy compared to traditional clinical variables and molecular features. It exhibited superior performance than other published models. By integrating CDI with relevant clinical features, a nomogram with excellent predictive performance was developed. LUAD patients with low CDI score had a higher immune modulators, TIDE scores and immune scores, indicating a better immunotherapy benefit. More importantly, we found that the regulation of antigen presentation is the crucial mechanism of PCD. SCG2 is a key molecule that inhibits the malignant progression of LUAD. CDI holds great potential as a robust and promising tool for enhancing clinical outcomes in patients with LUAD.
被引量:- 发表:1970
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Integrated analysis reveals NLRC4 as a potential biomarker in sepsis pathogenesis.
Sepsis remains a significant global health burden and contributor to mortality, yet the precise molecular mechanisms underlying the immune response are not fully elucidated. To gain insight into this issue, we performed a comprehensive analysis using a variety of techniques including bulk RNA sequencing, single-cell RNA sequencing, and enzyme-linked immunosorbent assay (ELISA). We performed enrichment analysis of differentially expressed genes in sepsis and healthy individuals by utilizing Gene Ontology (GO) analysis and indicated significant enrichment of immune-related response. Following Weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction analysis (PPI) were used to identify key immune-related hub genes and validated by ELISA to show that NLRC4 is highly expressed in sepsis. Additionally, an analysis of scRNA-seq data from newly diagnosed sepsis, sepsis diagnosis at 6 hours, and healthy samples demonstrates a significant increase in both the expression levels and proportions of NLRC4 in sepsis monocytes and neutrophils. In addition, using pySCENIC we identified upstream transcription factors that regulate NLRC4. Our study provides valuable insights into the identification of NLRC4 in peripheral blood as a potential candidate gene for the diagnosis and treatment of sepsis.
被引量:- 发表:1970
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Innate immune dynamics in the context of multisite EGFR mutations in lung adenocarcinoma.
Based on favorable outcomes and decreased propensity for lymph node and distant metastasis, multiple ground-glass nodules (GGNs) are now predominantly recognized as early-stage primary independent lung cancer. In this study, we discuss a case involving a patient with reoperative multifocal GGNs who was ultimately diagnosed with early multiple intrapulmonary metastases and multifocal primary lung cancers. This patient exhibited multisite epidermal growth factor receptor (EGFR) mutations, including the classical L858R, exon 19 deletion and the rare V834L variant. Despite a high tumor burden and the presence of various EGFR driver mutations, the patient experienced prolonged dormancy and exceptionally slow lesion growth, even without any systemic treatment. Our research indicates that the patient's immune response against the tumor remained robust throughout the disease course. Furthermore, we found that pathways associated with integrin-mediated cell extracellular matrix adhesion played a role in activating her innate immune responses and regulating tumor dormancy. Our findings suggest that the interplay between cancer cell mutations and the tumor microenvironment (TME) phenotype during tumor evolution contributed to this patient's prolonged survival. Integrating these aspects for lung tumor stratification is expected to improve predictions of growth potential and aid in clinical decision making.
被引量:- 发表:1970
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Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content.
Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE-/-) on the polarization and iron content of SM and its potential mechanisms. ApoE-/- was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1β, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE-/- caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE-/- can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.
被引量:- 发表:1970