INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2016
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IF 3.138
Ke Ming,Yun Chen,Fangke Yao,Jintong Shi,Jingjing Yang,Hongxu Du,Xunyi Wang,Yixuan Wang,Jiaguo Liu
To screen effective anti-duck hepatitis A virus (DHAV) drugs, we applied STMP-STPP method to prepare phosphorylated Codonopsis pilosula polysaccharide (pCPPS), the phosphorylation-modified product of Codonopsis pilosula polysaccharide (CPPS). The IR spectrum and field emission scanning electron microscope (FE-SEM) were subsequently used to analyze the structure of pCPPS. Several tests were conducted to compare the anti-DHAV activities of CPPS and pCPPS. The MTT method was used to compare the effect of the drugs on DHAV-infected duck embryonic hepatocytes (DEHs), and the Reed-Muench assay was employed to observe changes in the virulence of DHAV. We also applied real-time PCR to examine the relationship between virus replication and the expression of IFN-β. The results indicated that CPPS could not inhibit the replication of DHAV. In contrast, pCPPS increased the virus TCID 50 , inhibited viral replication and, accordingly, increased the survival rate of DEHs infected with DHAV. Because DHAV induced the expression of IFN-β, and the IFN-β expression level was positively associated with the number of DHAV, the reduction of IFN-β expression levels after pCPPS treatment demonstrated a decrease in the number of virus particles. These results indicated that pCPPS, which reduces the number of DHAV, was more effective than CPPS in anti-DHAV activity.
研究领域:
病毒学
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药理学
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分子生物学
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PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Jing P,Wang L,Qiu X,Chen L,Xie D,Yu Y,Li B,Yan S,Wang G,Zhong Z,Fu W.
Effective cancer immunotherapy relies on robust infiltration and sustained functionality of tumor-resident cytotoxic CD8 + T cells. Here we report a magnetic resonance imaging (MRI)-visible nanotheranostic that integrates redox modulation, inflammatory cell death, and innate immune sensitization to establish a self-amplifying pyroptosis-STING-IFN-β circuit for CD8 + T cell immunoactivation. The nanotheranostic is constructed through manganese ion (Mn 2+ )-catalyzed oxidative polymerization of polyphenols, enabling engineered reactive oxygen species (ROS) generation and localized metal ion availability. Functionally, intracellular ROS triggers caspase-3-dependent gasdermin E (GSDME) cleavage and pyroptosis, while concomitant mitochondrial perturbation increases cytosolic mitochondrial DNA (mtDNA) and sensitizes the cGAS-STING pathway to Mn 2+ -enhanced activation, resulting in IFN-β production. IFN-β further reinforces dendritic cells maturation and CD8 + T cells priming, whereas inflammatory pyroptosis amplifies mtDNA availability, together forming a self-amplifying positive-feedback circuit that magnifies antitumor immunity. In vivo , this coordinated mechanism promotes effective CD8 + T cells infiltration and memory formation. Owing to its high longitudinal relaxivity, the nanotheranostic enables clear T 1 -weighted MRI contrast with pronounced tumor accumulation and prolonged retention, supporting imaging-guided immunotherapy. This work presents a functional materials strategy that couples mechanistic immune amplification with diagnostic imaging, offering a conceptual framework for translatable immunotheranostics.
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PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
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IF 2.7
Xiaodong Liu,Tianyi Jiang,Huiyun Jin,Chenxi Yan,Yuqi Tong,Jiaquan Ding,Yaqi Li,Lian Huang,Zhaohui Zhang
Beryllium sulfate (BeSO 4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO 4 -induced inflammatory response in 16HBE cells, we established the BeSO 4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ 0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO 4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO 4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-β. This study revealed a novel mechanism of BeSO 4 -induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.
研究领域:
毒理学
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细胞生物学
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免疫学
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PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 17
·9179
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IF 13.3
Yue Yin,Shijie Zhao,Wei Li,Yuan Cui,Thanh Loc Nguyen,Ge Gao
Rationale : Dendritic cells (DCs) play a crucial role in adaptive immune responses; however, ex vivo differentiation strategies face operational complexities and reduced cellular viability. In situ reprogramming of resident cells into antigen-presenting cells represents a promising alternative approach for enhancing local immune responses. Methods : We initially introduce the novel concept of pseudo-DCs, in situ transforming intradermal fibroblasts into DC-like cells using an engineered exosome-loaded microneedle (MN) array. Specifically, engineered nano-protoplasts expressing interferon-beta (IFN-β) and loaded with varicella-zoster virus glycoprotein E (VZV gE) were used to stimulate DCs and derive immunostimulatory exosomes. These exosomes were integrated into a microarray-based delivery system for intradermal application. Results : The engineered exosomes (IdE@E) induced resident fibroblasts to upregulate DC surface co-stimulatory markers (CD80/86) and effectively present the model antigen. Transcriptome analysis also revealed significant upregulation of genes associated with immune response and antigen presentation in IdE@E-treated cells. In vivo studies demonstrated that MN array-delivered IdE@E effectively induced the expression of DC and activation markers from fibroblasts in dermis. Furthermore, MN array-delivered IdE@E significantly elevated the population of IFN-γ + CD8 + T cells in both lymph nodes and spleen, indicating enhanced local and systemic immune responses. Conclusions : This novel in situ reprogramming method represents a paradigm shift in precision immunotherapies, leveraging exosome-mediated cellular mimicry to enhance adaptive immunity without complete cellular transformation. This scalable framework holds significant promise for immunotherapy and could revolutionize personalized immunotherapy.
研究领域:
免疫学
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再生医学
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纳米医学
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药物递送
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细胞重编程
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疫苗
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULES
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2023
·Vol. 28
·期 9
·3740
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IF 4.6
Jibing Zhang,Xiao Cui,Yujiao Huang,Xiangdong Xu,Changshun Feng,Jun Li
Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-β and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8+T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm3, which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy.Keywords:STING;agonist;liposomes;antitumor;breast cancer
研究领域:
肿瘤学
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免疫疗法
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药学
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PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Di Zeng,Huifen Zhou,Haitong Wan,Jing Chen
Objective: Derived from Ma Huang Decoction in the Shang Han Lun, Yinhua Pinggan Granules (YHPG) are used in traditional Chinese medicine for treating influenza. This study highlights the gut microbiota’s role in intestinal damage and acute lung injury from influenza virus infection, offering insights into influenza A virus prevention and treatment through the gut-lung axis.Methods: Using a mouse model disrupted by a four-antibiotic regimen, we assessed survival, weight, lung, and spleen indices post-IAV infection. We evaluated lung and intestinal pathology, viral load, and protein expressions via H&E staining, RT-qPCR, and immunofluorescence. 16S rRNA sequencing and targeted metabolomics were utilized to uncover the impact of YHPG treatment on disrupted gut microbiota and its metabolites after H1N1 infection.Results: H&E staining showed severe lung and intestinal damage in IAV-infected mice with disrupted gut microbiota. Immunofluorescence results demonstrated that relative depletion of gut microbiota might exacerbate colonic barrier damage in IAV-infected mice. YHPG restored microbiota diversity, increasing SCFA-producing bacteria, aligning with metabolite changes. Western blot and RT-qPCR showed activation of the GPR43-MAVS-IRF3-IFN-I pathway, linked to SCFA regulation.Conclusion: YHPG alleviate influenza symptoms, promoting SCFA-producing bacteria and maintaining gut homeostasis. They modulate the GPR43-MAVS-IRF3-IFN-β pathway, suggesting novel treatment avenues for influenza through gut microbiota modulation.
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高影响因子
BIOMATERIALS
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2020
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IF 10.317
Jiayu Zhao,Sheng Ma,Yudi Xu,Xinghui Si,Haochen Yao,Zichao Huang,Yu Zhang,Haiyang Yu,Zhaohui Tang,Wantong Song,Xuesi Chen
STING (stimulator of interferon genes) signaling pathway has attracted considerable attention in cancer immunotherapy due to its capacity to boost vigorous antitumor immunity. However, the shortage of effective STING agonists limits the promotion of STING pathway in cancer treatment. Herein, we present an approach for in situ activation of STING pathway with nanoparticles delivered DNA-targeting chemo agents, based on the understanding that cytosol DNA is a pre-requisite for STING pathway activation. Through in vitro screening among several DNA-targeting chemo agents, we identified 7-ethyl-10-hydroxycamptothecin (SN38) as the most potent drug for stimulating interferon (IFN)-β secretion and proved that this process is mediated by the passage of DNA-containing exosomes from treated tumor cells to bone marrow-derived dendritic cells (BMDCs) and subsequent activation of the STING pathway. Furthermore, we designed a polymeric-SN38 conjugate that could self-assemble into nanoparticles (SN38-NPs) for in vivo application. The SN38-NPs formulation reduced toxicity of free SN38, effectively stimulated the activation of STING pathway in E0771 tumors, and resulted in a tumor suppression rate (TSR%) of 82.6%. Our results revealed a new mechanism of SN38 in cancer treatment and should inspire using more DNA-targeting agents, especially in nanoformulation, for activating STING pathway and cancer chemoimmunotherapy.
研究领域:
癌症免疫治疗
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药学
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纳米技术
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
·
IF 8.786
Qin Sheng,Huang Xianzhang,Qu Shaogang
Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.
研究领域:
病毒学
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免疫学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
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2024
·
IF 3.6
Wang Li,Cao Limin,Li Zhihong,Shao Zhugui,Chen Xia,Huang Zhicheng,He Xiaoxiao,Zheng Junke,Liu Li,Jia Xin-Ming,Xiao Hui
The cyclic GMP-AMP synthase (cGAS)–stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells’ cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-β response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear. In this study, we found that extracellular ATP, an immune regulatory molecule widely present in the tumor microenvironment, can potentiate cGAMP transfer, thereby boosting the STING signaling and IFN-β response in murine macrophages and fibroblasts. Notably, genetic ablation or chemical inhibition of murine volume-regulation anion channel LRRC8/volume-regulated anion channel (VRAC), a recently identified cGAMP transporter, abolished ATP-potentiated cGAMP transfer and STING-dependent IFN-β response, revealing a crucial role of LRRC8/VRAC in the cross-talk of extracellular ATP and cGAMP. Mechanistically, ATP activation of the P2X family receptors triggered Ca2+ influx and K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked K+ efflux alleviated the phosphorylation of VRAC’s obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated that the phosphorylation of S174 on LRRC8A could act as a checkpoint for VRAC in the steady state and a rheostat of ATP responsiveness. In an MC38-transplanted tumor model, systemically blocking CD39 and ENPP1, hydroxylases of extracellular ATP and cGAMP, respectively, elevated antitumor NK, NKT, and CD8+ T cell responses and restrained tumor growth in mice. Altogether, this study establishes a crucial role of ATP in facilitating LRRC8/VRAC transport cGAMP in the tumor microenvironment and provides new insight into harnessing cGAMP transfer for antitumor immunity.
研究领域:
免疫学
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癌症生物学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hai Li,Lingdi Niu,Jiaqing Wang,Qingru Chang,Shuhe Zhang,Jiaqi Wang,Jiankai Zeng,Mingchun Gao,Junwei Ge
Methicillin-resistant Staphylococcus aureus (MRSA) is rapidly spreading worldwide, emerging as a leading cause of bacterial infections in healthcare and community settings. This poses serious risks to human health. The shortage of novel antibiotics and the absence of effective vaccines make MRSA particularly challenging to treat. Existing vaccine development strategies often fail to provide early protection against infections, highlighting the urgent need for solutions. Herein, we propose a novel strategy combining trained immunity with a multi-epitope subunit vaccine to combat MRSA infections. We comprehensively evaluated the trained immune phenotypes induced by β-glucan from barley and curdlan. Macrophages trained with curdlan exhibited a more balanced inflammatory response compared to β-glucan from barley, expressing higher levels of IL-1β , IFN-β , TGF-β , and CCL2 upon secondary stimulation. Furthermore, curdlan-induced trained immunity rapidly provided excellent protection against S. aureus infection in mice. RNA-sequencing analysis revealed that curdlan modulates the Wnt signaling pathway in macrophages, resolves inflammation, and promotes tissue repair. When combined with one or two doses of S. aureus multivalent epitope antigen against MRSA infection, curdlan-induced trained immunity enhanced early protection and promoted recovery. Our study demonstrates the feasibility of combining trained immunity with vaccine protection against MRSA, providing a strategy against multi-drug resistant bacteria.
研究领域:
免疫学
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微生物学
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药理学
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疫苗学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-12
·
IF 14.7
Cui Zhanding,Liu Jinlong,Xie Chong,Wang Tao,Sun Pu,Wang Jinlong,Li Jiaoyang,Li Guoxiu,Qiu Jicheng,Zhang Ying,Li Dengliang,Sun Ying,Yin Juanbin,Li Kun,Zhao Zhixun,Yuan Hong,Bai Xingwen,Ma Xueqing,Li Pinghua,Fu Yuanfang,Bao Huifang,Li Dong,Zhang Qiang,Liu Zaixin,Cao Yimei,Zhang Jing,Lu Zengjun
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.
研究领域:
兽医学
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分子生物学
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药理学
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病毒学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Luo Zhuo,Liu Li-Fang,Wang Xiao-Hua,Li Wen,Jie Chong,Chen Huan,Wei Fan-Qin,Lu Dan-Hua,Yan Chang-Yu,Liu Bo,Kurihara Hiroshi,Li Yi-Fang,He Rong-Rong
Stress has been proven to modulate an individual’s immune system through the release of pituitary and adrenal hormones such as the catecholamines, growth hormone, and glucocorticoids. These signal molecules can significantly alter the host immune system and make it susceptible to viral infection. In this study, we investigate whether epigoitrin, a natural alkaloid from Isatis indigotica, provides protection against influenza infection by reducing the host’s susceptibility to influenza virus under stress and its underlying mechanism. To support it, the mouse restraint stress model and the corticosterone-induced stress model were employed. Our results demonstrated that epigoitrin significantly decreased the susceptibility of restraint mice to influenza virus, evidenced by lowered mortality, attenuated inflammation, and decreased viral replications in lungs. Further results revealed that epigoitrin reduced the protein expression of mitofusin-2 (MFN2), which elevated mitochondria antiviral signaling (MAVS) protein expression and subsequently increased the production of IFN-β and interferon inducible transmembrane 3 (IFITM3), thereby helping to fight viral infections. In conclusion, our study indicated that epigoitrin could reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.
研究领域:
免疫学
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病毒学
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药理学
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DOI
PubMed
高影响因子
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