Bioactive Materials
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2024
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IF 18
Dongdong Xu,Jun Hu,Jiawei Mei,Jun Zhou,Zhengxi Wang,Xudong Zhang,Quan Liu,Zheng Su,Wanbo Zhu,Hongjian Liu,Chen Zhu
Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a "cold tumor"-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.
研究领域:
骨科手术
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免疫学
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纳米技术
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传染病
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF VIROLOGY
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2024
·Vol. 169
·期 11
·1-10
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IF 2.5
Jiao Qian,Zhu Shu,Liao Baolin,Liu Huiyuan,Guo Xiaoyan,Wu Lina,Chen Chuming,Peng Liang,Xie Chan
NLR family member X1 (NLRX1) is an important member of the NOD-like receptor (NLR) family and plays unique roles in immune system regulation. Patients with hepatitis B virus (HBV) infection are more likely to have the NLRX1 mutation p.Arg707Cys than healthy individuals. It has been reported that NLRX1 increases the infection rate of HBV in HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). However, the role of NLRX1 mutation ( p.Arg707Cys ) in hepatitis remains unclear. We constructed Huh7 cells that stably overexpressed NTCP, using LV003 lentivirus. First, wild-type (WT) and mutant (MT) NLRX1 overexpression plasmids were constructed. The MT plasmid contained a point mutation at position 707 of the WT overexpression plasmid. Then, Huh7-NTCP cells were transfected with the WT or MT NLRX1 overexpression plasmid, and subsequent NLRX1 expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. HBV RNA levels were determined using RT-qPCR. HBsAg and HBcAg levels were confirmed immunohistochemically. Interferon alpha (IFN-α), interleukin 6 (IL-6), and type I interferon beta (IFN-β) levels were determined using enzyme-linked immunosorbent assay kits. p-p65, p-interferon regulatory factor (IRF) 3, and p-IRF7 expression levels were examined using western blot. The interaction of NLRX1 and retinoic acid-inducible gene (RIG)-1/mitochondrial antiviral signaling (MAVS) protein was confirmed by coimmunoprecipitation. The interaction of NLRX1 with IFN-α, IL-6, or IFN-β was analyzed by dual luciferase reporter gene assay. The levels of HBV RNA, HBsAg, and HBcAg in infected cells transfected with the WT NLRX1 or MT NLRX1 expression plasmid were higher than those in the untransfected control group; and these levels were lower in the cells transfected with MT NLRX1 than in those transfected with WT NLRX1. The levels of IFN-α, IFN-β, IL-6, p-p65, p-IRF3, and p-IRF7 were lower in cells transfected with WT NLRX1 or MT NLRX1 than in control cells. The levels of IFN-β, p-p65, p-IRF3, and p-IRF7 were higher in cells transfected with MT NLRX1 than in those transfected with WT NLRX1. Moreover, NLRX1 competitively inhibited RIG1 binding to MAVS, but the mutation in MT NLRX1 reduced this inhibitory effect. In addition, NLRX1 decreased the promoter activity of IFN-α, IFN-β, and IL-6. Our findings revealed that NLRX1 is a regulatory factor that inhibits the anti-HBV ability of hepatocytes and that the mutation p.Arg707Cys in NLRX1 suppresses HBV infection and activates the IFN/nuclear factor κB pathway.
研究领域:
免疫学
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病毒学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Shengjie Sun,Mian Yu,Liu Yu,Wenxin Huang,Meishu Zhu,Yanan Fu,Lingchen Yan,Qiang Wang,Xiaoyuan Ji,Jing Zhao,Meiying Wu
Photodynamic therapy (PDT)-mediated antitumor immune response depends on oxidative stress intensity and subsequent immunogenic cell death (ICD) in tumor cells, yet the inherent antioxidant system restricts reactive oxygen species (ROS)-associated oxidative damage , which is highly correlated with the upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and the downstream products, such as glutathione (GSH). Herein, to overcome this dilemma, we designed a versatile nanoadjuvant ( [email protected] ) to enhance the sensitivity of tumor cells to oxidative stress via Nrf2-specific small interfering RNA (siNrf2). The constructed [email protected] could significantly amplify photooxidative stress and achieve robust DNA oxidative damage, activating the stimulator of interferon genes (STING)-dependent immune-sensing to produce interferon-β (IFN-β). Additionally, [email protected] together with laser irradiation reinforced tumor immunogenicity by exposing or releasing damage-associated molecular patterns (DAMPs), showing the prominent adjuvant effect for promoting dendritic cell (DC) maturation and T-lymphocyte activation and even alleviating the immunosuppressive microenvironment to some extent.
研究领域:
肿瘤学
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免疫学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Weichong He,Wei Lv,Linfeng Liu,Yue Gong,Kefan Song,Jiangna Xu,Wei Zhao,Shengnan Li,Zhiyi Min,Qinhua Chen,Jiaqing Yin,Yuqin Chen,Hufeng Fang,Hongliang Xin,Xiangming Fang
Glioblastoma, the most prevalent malignant brain tumor, is a lethal threat to human health, with aggressive and infiltrative growth characteristics that compromise the clinical treatment. Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO2-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO2) which were coated with a vitamin D3-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO2-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8+T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a “cold” tumor to a “hot” tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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药学
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产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Niu Lingdi,Li Hai,Guo Junjie,Jia Zheng,Chang Qingru,Liu Ning,Zhang Shuhe,Ge Junwei
The gut microbiota plays a complex role in immune system maturation and function. The induction of memory in innate immune cells appears to be part of a co-adaptation between the host and microbiome. As important gut commensals, certain Lactobacillus have been shown to induce innate immune memory. However, the universality, phenotypic characteristics, mechanisms of Lactobacillus -induced innate immune memory, and its potential applications in vaccine immunology remain poorly understood. Here, we discovered that specific strains of the gut commensal Lactobacillus can induce innate immune memory, resulting in a more balanced trained immunity phenotype through SOCS activation. Upon secondary stimulation, macrophages exhibited increased expression of IL-6 , IL-1β , IL-10 , IL-12 , IFN-β , and TGF-β . Peptidoglycan and components in the secretome sensitive to pancreatic enzymes were identified as key elements in inducing trained immunity. Furthermore, mice that underwent training demonstrated rapid resistance to S. aureus infection. Additionally, Lactobacillus -induced trained immunity significantly enhanced the protective efficacy of vaccines against MRSA. Our findings demonstrate that certain Lactobacillus strains can activate non-classical trained immunity, offering potential for enhancing vaccine efficacy. Our study provides new insights into the role of some gut commensals in immune modulation and suggests a novel approach to vaccine enhancement through trained immunity induced by specific gut commensals.
研究领域:
免疫学
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微生物组研究
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疫苗学
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固有免疫
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分子生物学
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宿主-微生物相互作用
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Jing Feng,Yiting Liu,Xiaoran Zheng,Min Gao,Li Wang,Lígia R. Rodrigues,Yuting Wen,Hangcheng Pan,Gege Li,Longjiang Zhang,Bing Wan,Yunlei Zhang
The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4 + and CD8 + cytotoxic T cells and the secretion of interferon-β, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.
研究领域:
癌症治疗
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免疫疗法
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生物医学工程
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药理学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
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