keyword
https://read.qxmd.com/read/38489367/treatment-with-sirnas-is-commonly-associated-with-gpx4-up-regulation-and-target-knockdown-independent-sensitization-to-ferroptosis
#21
JOURNAL ARTICLE
Anne von Mässenhausen, Marlena Nastassja Schlecht, Kristina Beer, Francesca Maremonti, Wulf Tonnus, Alexia Belavgeni, Shubhangi Gavali, Karolin Flade, Joel S Riley, Nadia Zamora Gonzalez, Anne Brucker, Jorunn Naila Becker, Mirela Tmava, Claudia Meyer, Mirko Peitzsch, Christian Hugo, Florian Gembardt, Jose Pedro Friedmann Angeli, Stefan R Bornstein, Stephen W G Tait, Andreas Linkermann
Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed...
March 15, 2024: Science Advances
https://read.qxmd.com/read/38486772/insufficient-phosphorylation-of-stat5-in-tregs-inhibits-the-expression-of-blimp-1-but-not-irf4-reduction-the-proportion-of-tregs-in-pediatric-aplastic-anemia
#22
JOURNAL ARTICLE
Lifen Huang, Junbin Huang, Nannan Tang, Hongman Xue, Shaofen Lin, Su Liu, Qihui Chen, Yinsi Lu, Qian Liang, Yun Wang, Qingqing Zhu, Guoxing Zheng, Yun Chen, Chengming Zhu, Chun Chen
Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38484578/ifitm1-and-ifitm2-inhibit-the-replication-of-senecavirus-a-by-positive-feedback-with-rig-i-signaling-pathway
#23
JOURNAL ARTICLE
Huizi Li, Ming Chen, Tingting Zheng, Xiaoling Lei, Cunhao Lin, Shuo Li, Jiacong Mo, Zhangyong Ning
The role of host factors in the replication of emerging senecavirus A (SVA) which induced porcine idiopathic vesicular disease (PIVD) distributed worldwide remains obscure. Here, interferon-induced transmembrane (IFITM) protein 1 and 2 inhibit SVA replication by positive feedback with RIG-I signaling pathway was reported. The expression levels of IFITM1 and IFITM2 increased significantly in SVA infected 3D4/21 cells. Infection experiments of cells with over and interference expression of IFITM1 and IFITM2 showed that these two proteins inhibit SVA replication by regulating the expression of interferon beta (IFN-β), IFN-stimulated gene 15 (ISG-15), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), IFN regulatory factor-3 (IRF3), and IRF7...
March 11, 2024: Veterinary Microbiology
https://read.qxmd.com/read/38480774/interferon-%C3%AE-in-the-tumor-microenvironment-promotes-the-expression-of-b7h4-in-colorectal-cancer-cells-thereby-inhibiting-cytotoxic-t-cells
#24
JOURNAL ARTICLE
Zhi-Liang Jing, Guang-Long Liu, Na Zhou, Dong-Yan Xu, Na Feng, Yan Lei, Li-Li Ma, Min-Shan Tang, Gui-Hui Tong, Na Tang, Yong-Jian Deng
The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells...
March 13, 2024: Scientific Reports
https://read.qxmd.com/read/38479600/the-aryl-hydrocarbon-receptor-interacting-protein-in-cancer-and-immunity-beyond-a-chaperone-protein-for-the-dioxin-receptor
#25
REVIEW
Sarah A Kazzaz, John Tawil, Edward W Harhaj
The aryl hydrocarbon receptor (AhR) interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the AhR-AIP-Hsp90 cytoplasmic complex. In addition to regulating AhR and the xenobiotic response, AIP has been linked to various aspects of cancer and immunity that will be the focus of this review article. Loss of function AIP mutations are associated with pituitary adenomas, suggesting that AIP acts as a tumor suppressor in the pituitary gland. However, the tumor suppressor mechanisms of AIP remain unclear, and AIP can exert oncogenic functions in other tissues...
March 11, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38474113/notch1-related-leukoencephalopathy-a-novel-variant-and-literature-review
#26
Stefania Della Vecchia, Alessandra Tessa, Rosa Pasquariello, Luis Seabra, Yanick J Crow, Roberta Battini
NOTCH1 -related leukoencephalopathy is a new diagnostic entity linked to heterozygous gain-of-function variants in NOTCH1 that neuroradiologically show some overlap with the inflammatory microangiopathy Aicardi-Goutières syndrome (AGS). To report a 16-year-old boy harbouring a novel NOTCH1 mutation who presented neuroradiological features suggestive of enhanced type I interferon signalling. We describe five years of follow-up and review the current literature on NOTCH1 -related leukoencephalopathy. Clinical evaluation, standardised scales (SPRS, SARA, CBCL, CDI-2:P, WISCH-IV and VABS-2) and neuroradiological studies were performed, as well as blood DNA analysis...
March 1, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38472498/modulation-of-plasmacytoid-dendritic-cell-and-cd4-t-cell-differentiation-accompanied-by-upregulation-of-the-cholinergic-anti-inflammatory-pathway-induced-by-enterovirus-71
#27
JOURNAL ARTICLE
Li Li, Rong-Wei Huang, Xiao-Ning Liu, Xiao-Yi Xiang, Yuan-Tao Zhou, Xing-Xing Feng, Lv-Yuan Tao, Jia Yu, Qin Yi, Yan-Chun Wang, Xiao-Mei Liu
Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells...
March 13, 2024: Archives of Virology
https://read.qxmd.com/read/38471722/celastrol-ameliorates-lupus-by-promoting-apoptosis-of-autoimmune-t-cells-and-preventing-autoimmune-response-in-mrl-lpr-mice
#28
JOURNAL ARTICLE
Tianhong Xie, Hongliang Rui, Huiqiang Liu, Xin Liu, Xiang Liu, Ping Li
OBJECTIVE: Celastrol is a bioactive constituent extracted from Tripterygium wilfordii (thunder god vine). It has been demonstrated to have a therapeutic effect on experimental disease models for chronic inflammatory and immune disorders. In the present study, we investigated whether and how celastrol exerts a regulatory effect on the autoimmune response in MRL/lpr mice. METHODS: We performed an in vivo study to determine the therapeutic effects of celastrol in MRL/lpr mice and then further investigated the underlying mechanism of celastrol in the regulation of the autoimmune response in MRL/lpr mice...
March 11, 2024: Lupus Science & Medicine
https://read.qxmd.com/read/38466881/berberine-alleviates-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-modulating-the-gut-microbiota
#29
JOURNAL ARTICLE
Hao Yang, Qingqing Liu, Haixia Liu, Xing Kang, Haixia Tian, Yongbo Kang, Lin Li, Xiaodan Yang, Peng Ren, Xiaoyu Kuang, Xiaohui Wang, Linzhi Guo, Mingwei Tong, Jieqiong Ma, Weiping Fan
BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment...
April 1, 2024: Hepatology Communications
https://read.qxmd.com/read/38461415/hdac5-enhances-irf3-activation-and-is-targeted-for-degradation-by-protein-c6-from-orthopoxviruses-including-monkeypox-virus-and-variola-virus
#30
JOURNAL ARTICLE
Yongxu Lu, Yiqi Zhao, Chen Gao, Shreehari Suresh, Jinghao Men, Amelia Sawyers, Geoffrey L Smith
Histone deacetylases (HDACs) regulate gene expression and innate immunity. Previously, we showed that HDAC5 is degraded during Vaccinia virus (VACV) infection and is a restriction factor for VACV and herpes simplex virus type 1. Here, we report that HDAC5 promotes interferon regulatory factor 3 (IRF3) activation downstream of Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 or Sendai virus-mediated stimulation without requiring HDAC activity. Loss of HDAC5-mediated IRF3 activation is restored by re-introduction of HDAC5 but not HDAC1 or HDAC4...
March 9, 2024: Cell Reports
https://read.qxmd.com/read/38453210/flavonoid-extracted-from-epimedium-attenuate-cgas-sting-mediated-diseases-by-targeting-the-formation-of-functional-sting-signalosome
#31
JOURNAL ARTICLE
Yan Wang, Guang Xu, Jincai Wen, Xiaomei Zhao, Huanying Zhao, Guiji Lv, Yingjie Xu, Ye Xiu, Junjie Li, Simin Chen, Qing Yao, Yuanyuan Chen, Lina Ma, Xiaohe Xiao, Junling Cao, Zhaofang Bai
Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear...
March 7, 2024: Immunology
https://read.qxmd.com/read/38452958/the-antiviral-role-of-largemouth-bass-sting-against-iridovirus-infection
#32
JOURNAL ARTICLE
Xinmei Yang, Yuyun Dong, Yu Wang, Shanxin Liu, Xiaohong Huang, Youhua Huang, Qiwei Qin
Stimulator of interferon gene (STING) plays a crucial role in the innate immune response against viral and bacterial pathogens. However, its function in largemouth bass iridovirus (LMBV) infection remains uncertain. Here, a STING homolog (MsSTING) from largemouth bass (Micropterus salmoides) was cloned and characterized. MsSTING encoded a 407-amino-acid polypeptide, which shared 84.08% and 41.45% identity with golden perch (Perca flavescens) and human (Homo sapiens) homologs, respectively. MsSTING contained four transmembrane domains and a conserved C-terminal domain...
March 5, 2024: Fish & Shellfish Immunology
https://read.qxmd.com/read/38451436/interferon-regulatory-factor-5-gene-polymorphisms-and-mrna-expression-levels-are-associated-with-neuromyelitis-optica-spectrum-disorder
#33
JOURNAL ARTICLE
Gaoning Wang, Liu Jing, Ying Wang, Arshad Mehmood, Huining Zhang, Ruoyi Guo, Lu Zhang, Bin Li
Interferon regulatory factor 5 (IRF5) is a critical transcription factor in the toll-like receptor signaling pathway. It is associated with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. However, the relationship between the functional single nucleotide polymorphisms (SNPs) of IRF5 and its mRNA expression level in patients with neuromyelitis optica spectrum disorder remains unclear. The present study aimed to investigate the relationship between polymorphisms and mRNA expression levels of the IRF5 gene with the incidence of neuromyelitis optica spectrum disorder (NMOSD) in northern Chinese Han people...
March 7, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38449802/human-adenovirus-type-3-restores-pharmacologically-inhibited-exosomal-cargo-in-lung-carcinoma-cells
#34
JOURNAL ARTICLE
Ayodeji O Ipinmoroti, Rachana Pandit, Brennetta J Crenshaw, Brian Sims, Qiana L Matthews
Introduction: Drug repurposing is fast growing and becoming an attractive approach for identifying novel targets, such as exosomes for cancer and antiviral therapy. Exosomes are a specialized class of extracellular vesicles that serve as functional mediators in intercellular communication and signaling that are important in normal physiological functions. A continuously growing body of evidence has established a correlation between the abnormal release of exosomes with various viral disease pathologies including cancer...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38448411/the-rna-m-6-a-reader-igf2bp3-regulates-nfat1-irf1-axis-mediated-anti-tumor-activity-in-gastric-cancer
#35
JOURNAL ARTICLE
Lichen Ge, Yalan Rui, Cheng Wang, Yingmin Wu, Hongsheng Wang, Junjun Wang
N6 -methyladenosine (m6 A) and its associated reader protein insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) are involved in tumor initiation and progression via regulating RNA metabolism. This study aims to investigate the biological function and clinical significance of IGF2BP3 in gastric cancer (GC). The clinical significance of IGF2BP3 was evaluated using tumor related databases and clinical tissues. The biological role and molecular mechanism of IGF2BP3 in GC progression were investigated by multi-omics analysis including Ribosome sequence (Ribo-seq), RNA sequence (RNA-seq) and m6 A sequence (m6 A-seq) combined with gain- and loss- of function experiments...
March 6, 2024: Cell Death & Disease
https://read.qxmd.com/read/38443768/toxoplasma-gondii-ist-suppresses-inflammatory-and-apoptotic-responses-by-inhibiting-stat1-mediated-signaling-in-ifn-%C3%AE-tnf-%C3%AE-stimulated-hepatocytes
#36
JOURNAL ARTICLE
Seung-Hwan Seo, Ji-Eun Lee, Do-Won Ham, Eun-Hee Shin
The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection...
February 2024: Parasites Hosts Dis
https://read.qxmd.com/read/38440980/human-otic-progenitor-cell-models-of-congenital-hearing-loss-reveal-potential-pathophysiologic-mechanisms-of-zika-virus-and-cytomegalovirus-infections
#37
JOURNAL ARTICLE
Alfred T Harding, Karen Ocwieja, Minjin Jeong, Yichen Zhang, Valerie Leger, Nairuti Jhala, Konstantina M Stankovic, Lee Gehrke
UNLABELLED: Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. Viruses correlated with congenital hearing loss include human cytomegalovirus (HCMV) and Zika virus (ZIKV), which causes congenital Zika syndrome. The mechanisms by which HCMV and ZIKV infections cause hearing loss are poorly understood. It is challenging to study human inner ear cells because they are encased in bone and also scarce as autopsy samples. Recent advances in culturing human stem cell-derived otic progenitor cells (OPCs) have allowed us herein to describe successful in vitro infection of OPCs with HCMV and ZIKV, and also to propose potential mechanisms by which each viral infection could affect hearing...
March 5, 2024: MBio
https://read.qxmd.com/read/38439718/assessing-interferon-regulatory-factor-4-complex-formation-differential-behavior-of-homocomplexes-versus-heterocomplexes-induced-by-mutations
#38
JOURNAL ARTICLE
Yupeng Li, Setoka Hirano, Katsuya Sato, Masatake Osawa, Hitoshi Nagaoka
Interferon regulatory factor 4 (IRF4) is a crucial transcription factor that plays a vital role in lymphocyte development, including in the fate-determining steps in terminal differentiation. It is also implicated in the development of lymphoid tumors such as multiple myeloma and adult T-cell leukemia. IRF4 can form a homodimer and multiple heterocomplexes with other transcription factors such as purine-rich box1 and activator protein 1. Each protein complex binds to specific DNA sequences to regulate a distinct set of genes...
March 5, 2024: Biochemistry
https://read.qxmd.com/read/38436707/role-of-cd4-t-cells-for-regulating-splenic-myelopoiesis-and-monocyte-differentiation-after-experimental-myocardial-infarction
#39
JOURNAL ARTICLE
Nadine Gladow, Claudia Hollmann, Johannes Weirather, Xin Ding, Matthias Burkard, Sabrina Uehlein, Richa Bharti, Konrad Förstner, Thomas Kerkau, Niklas Beyersdorf, Stefan Frantz, Gustavo Ramos, Ulrich Hofmann
Myocardial infarction (MI) induces the generation of proinflammatory Ly6Chigh monocytes in the spleen and the recruitment of these cells to the myocardium. CD4+ Foxp3+ CD25+ T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4+ T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4+ T-cell deficient animals...
March 4, 2024: Basic Research in Cardiology
https://read.qxmd.com/read/38433025/atherosclerosis-deteriorates-liver-ischemia-reperfusion-injury-via-interferon-regulatory-factor-1-overexpression-in-a-murine-model
#40
JOURNAL ARTICLE
Ryosuke Nakano, Ichiya Chogahara, Masahiro Ohira, Kouki Imaoka, Saki Sato, Tomoaki Bekki, Koki Sato, Yuki Imaoka, Doskali Marlen, Yuka Tanaka, Hideki Ohdan
BACKGROUND: Abdominal aortic calcification (AAC) is associated with cardiovascular-related mortality, along with an elevated risk of coronary, cerebrovascular, and cardiovascular events. Notably, AAC is strongly associated with poor overall and recurrence free survival posthepatectomy for hepatocellular carcinoma. Despite the acknowledged significance of atherosclerosis in systemic inflammation, its response to ischemia/reperfusion injury (IRI) remains poorly elucidated. In this study, we aimed to clarify the impact of atherosclerosis on the liver immune system using a warm IRI mouse model...
March 2, 2024: Transplantation Proceedings
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