CELLULAR IMMUNOLOGY
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2025
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IF 2.9
Yiqi Wang,Xiuhua Zhang,Jiannan Zhang,Mingbo Zhao,Yang Chong,Quankuan Gu,Xianglin Meng,Mingyan Zhao
Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties. This study aims to investigate the effects of ANAPC5 on ALI and its underlying molecular mechanism. In the lung tissue of an ALI mouse model induced by lipopolysaccharide (LPS) administration, we observed downregulation of ANAPC5. Through both in vivo and in vitro experiments, we assessed the effect of ANAPC5 on lung injury by conducting pathological analysis and molecular biological detection. ANAPC5 overexpression alleviated inflammatory cell infiltration, reduced alveolar wall thickening, suppressed pulmonary inflammation, and decreased the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue of the ALI model. Moreover, ANAPC5 inhibited M1 polarization and promoted M2 polarization of macrophages both in vitro and in vivo . We also found that ANAPC5 significantly suppressed the activation and expression of the epidermal growth factor receptor (EGFR) through inducing its ubiquitination in macrophages. In LPS-induced M1 macrophages, the presence of EGFR significantly decreased CD24 expression, followed by reversing the inhibitory effects of ANAPC5 on inflammatory responses and macrophage polarization. Collectively, our findings suggest that ANAPC5 serves as a therapeutic molecular target that mitigates ALI through regulating macrophage M1/M2 polarization via the EGFR/CD24 axis.
研究领域:
免疫学
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呼吸病学
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分子生物学
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炎症反应调控
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转化医学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-19
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IF 14.7
Zhang Weiqi,Zeng Yinghua,Xiao Qiuqun,Wu Yuanyuan,Liu Jiale,Wang Haocheng,Luo Yuting,Zhan Jie,Liao Ning,Cai Yanbin
Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics for blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, a peptide-antibody combo-supramolecular in situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) is described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding and enzyme-triggered reactions. By simultaneously blocking CD47 and CD24 signaling, PAC-SABI enhances the phagocytic ability of macrophages in vitro and in vivo, promoting anti-tumor responses in breast and pancreatic cancer mouse models. Moreover, building on the foundation of PAC-SABI-induced macrophage repolarization and increased CD8 + T cell tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 tumor progression, prolonging survival rate. The in vivo construction of PAC-SABI-based nano-architectonics provides an efficient platform for bridging innate and adaptive immunity to maximize therapeutic potency.
研究领域:
免疫学
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肿瘤学
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生物技术
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
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2024
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IF 8.2
Mingzhu Zhao,Qin Li,Yan Zhao,Hanlin Zhou,Yuntian Yan,Rong-Mei Kong,Qingqing Tan,Weiheng Kong,Fengli Qu
Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dual-aptamer targeted exosome-based strategy for ovarian cancer screening. In brief, a DNA ternary polymer with aptamers targeting EpCAM and CD24 was designed to present a logic gate reaction upon recognizing ovarian cancer exosomes, triggering a rolling circle amplification chemiluminescent signal. A dynamic detection range of 6 orders of magnitude was achieved by quantifying exosomes. Moreover, for clinical samples, this strategy could accurately differentiate exosomes from healthy persons, other cancer patients, and ovarian cancer patients, enabling promising in situ detection. By accurately selecting biomarkers and constructing a dual-targeted exosomal protein detection strategy, the limitation of insufficient specificity of traditional protein markers was circumvented. This work contributed to the development of exosome-based prognosis monitoring in ovarian cancer through the identification of disease-specific exosome protein markers.
研究领域:
肿瘤学
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分子生物学
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诊断学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2022
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IF 8.101
Jin Li,Zi-Hui Wang,Ya-Min Dang,Dan-Ni Li,Zhen Liu,Da-Peng Dai,Jian-Ping Cai
MTH1 protein can sanitize the damaged (d)NTP pool and MTH1 inhibitors have been developed to impede the growth of rapidly proliferating tumor cells; however, the effect of MTH1 inhibition on breast cancer stemness has not been reported yet. Here, we constructed breast cancer cell lines with the stable depletion of MTH1. MTH1 suppression clearly increased the ratio of CD44 + CD24 −/low subpopulations and promoted the formation of tumorspheres in MCF7 and T47D cells. RNA expression profiling, RT–qPCR and Western blotting showed the upregulation of master stem cell transcription factors Sox2 , Oct4 and Nanog in MTH1 knockdown cells. GSEA suggested and Western blotting verified that MTH1 knockdown increased the expression of phosphorylated STAT3 (Tyr705). Furthermore, we indirectly demonstrated that the increased concentration of 8-oxo-dGTP and 8-oxo-GTP in MTH1 -knockdown cells and exogenous 8-oxoGTP, rather than 8-oxo-dGTP, could significantly increase the phosphorylation of STAT3. In conclusion, this work indicates that MTH1 inhibition increased the proportion of breast cancer stem cells (BCSCs) and promoted stemness properties in MCF7 cells.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Tao Hu,Haoyu Xiao,Shanling Ji,Zihao Wu,Yunlin Quan,Wang Zhen,Xiao Li,Jianxiong Zhu,Zhonghua Ni
In early cancer diagnosis, extracellular vesicles (EVs) are more advantageous than circulating tumor cells due to their smaller size, greater stability, and enhanced tissue penetration. These qualities lead to higher EV concentrations in body fluids, facilitating early detection. This study leverages surface-enhanced Raman scattering (SERS) for EVs detection, employing a novel biosensor made with a molybdenum disulfide (MoS2) composite film on silicon, noted for its high sensitivity and easy labeling. This biosensor efficiently measures EVs concentrations and precisely detects three specific proteins on ovarian cancer EVs simultaneously (CD63, CD24, CA125). Using the ovarian cancer cell line HO8910, the sensor demonstrated a detection limit of 1.4×104 particles/mL and a wide linear range of 3.4×104 particles/mL to 3.4×108 particles/mL . It also effectively discriminated between serum samples from healthy individuals and ovarian cancer patients at different stages. Additionally, machine learning was applied to analyze detection data, resulting in a diagnostic model with 97.78% prediction accuracy. This highlights the sensor's potential in revolutionizing early cancer detection and establishing new diagnostic models.
研究领域:
生物医学工程
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肿瘤学
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生物化学
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纳米技术
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机器学习
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Zhenmei Yang,Ying Liu,Kun Zhao,Weiqiang Jing,Lin Gao,Xianghui Dong,Yan Wang,Maosen Han,Chongdeng Shi,Chunwei Tang,Peng Sun,Rui Zhang,Zhipeng Fu,Jing Zhang,Danqing Zhu,Chen Chen,Xinyi Jiang
Hepatocellular carcinoma (HCC) is a prevalent and lethal disease, and tumor regression rarely occurs in advanced HCC patients due to limited effective therapies. Given the enrichment of macrophages in HCC and their role in tumor immunity, transforming them into chimeric antigen receptor macrophages (CAR-Ms) is thought to increase HCC cell-directed phagocytosis and tumoricidal immunity. To test this hypothesis, mRNA encoding CAR is encapsulated in a lipid nanoparticle (LNP) that targets liver macrophages. Notably, the LNPs adsorb specific plasma proteins that enable them to target HCC-associated macrophages. Moreover, mRNA encoding Siglec-G lacking ITIMs (Siglec-GΔITIMs) is codelivered to liver macrophages by LNP to relieve CD24-mediated CAR-Ms immune suppression. Mice treated with LNPs generating CAR-Ms as well as CD24-Siglec-G blockade significantly elevate the phagocytic function of liver macrophages, reduce tumor burden and increase survival time in an HCC mouse model. Arguably, our work suggests an efficacious and flexible strategy for the treatment of HCC and warrants further rigorous evaluation in clinical trials .
研究领域:
肿瘤学
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免疫治疗
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分子生物学
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纳米技术
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DOI
PubMed
高影响因子
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