ACS Nano
·
2025
·
IF 16
Yichao Lu,Xinyu Shan,Jiaxin Huang,Huanli Zhou,Ying Zhu,Sijie Wang,Zhenyu Luo,Xu Liu,Xuemeng Guo,Yingying Shi,Yilong Hu,Huihui Liu,Junlei Zhang,Ping Huang,Lihua Luo,Jian You
Atopic dermatitis (AD) is a recurrent and chronic inflammatory skin condition characterized by a high lifetime prevalence and significant impairment of patients’ quality of life, primarily due to intense itching and discomfort. However, current pharmacological interventions provide only moderate efficacy and are frequently accompanied by adverse side effects. The immune-pathogenesis of AD involves dysregulation of the Th2 immune response and exacerbation of inflammation related to excessive reactive oxygen species (ROS). Therefore, to address these issues, in this study, we targeted the upstream pathogenesis by designing a pro-Th1 adjuvant nanoemulsion loaded with poly(I:C) and encapsulated with the ROS-scavenger vitamin E, termed PV-NE. PV-NE effectively rebalanced the Th1/Th2 immune response and reduced ROS levels both in vivo and ex vivo, leading to the restoration of immune balance in AD-affected skin and alleviation of symptoms such as lichenification and erythematous patches. In conclusion, our development of the reductive adjuvant nanosystem PV-NE demonstrates its biocompatibility and efficacy in combating AD progression without the use of immunosuppressant glucocorticoids. This has the potential to significantly impact the design and enhancement of pharmacotherapy in future clinical research aimed at curing AD.
研究领域:
皮肤病学
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免疫学
·
纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2024
·Vol. 10
·期 1
·1-14
·
IF 6.1
Sun Bao-Ye,Wang Zhu-Tao,Chen Ke-Zhu,Song Yang,Wu Jing-Fang,Zhang Dai,Sun Guo-Qiang,Zhou Jian,Fan Jia,Hu Bo,Yi Yong,Qiu Shuang-Jian
Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8 + T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症免疫治疗
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Qunfang Yang,Tao Liu,Haiping Zheng,Zechen Zhou,Yan Huang,Honglin Jia,Shixiang Fu,Xuan Zhang,Haigang Zhang,Ya Liu,Xiaohong Chen,Wenjun Shan
The efficacy of immunotherapy combined with other therapeutic modalities in the management of cancer has been extensively studied. However, no effective strategy to improve the antitumor effects of immunotherapy at the tumor site has been developed. In this study, we describe a nanoformulation (CP) that integrates ferroptosis-inducing cannabinoid nanoparticles with immunostimulatory Poly(I:C) to enhance antitumor immune responses by activating ferroptosis-immunotherapy pathways. The results indicated that CP nanoformulation effectively induced ferroptosis , cellular immunogenic death, and anti-tumor immune responses which initiate T cell responses leading to the inhibition of established tumors. In addition, CP nanoformulations reversed the tumor immunosuppressive microenvironment and promoted tumor ferroptosis. These results indicated that the self-amplifying nanoformulation may be an effective strategy for broad-spectrum cancer immunotherapy .
研究领域:
癌症研究
·
免疫学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Han Sun,Xue-Kai Wang,Jian-Rui Li,Mei Tang,Hu Li,Lei Lei,Hong-Ying Li,Jing Jiang,Jia-Yu Li,Biao Dong,Jian-Dong Jiang,Zong-Gen Peng
The cell adhesion between leukocytes and endothelial cells plays an important balanced role in the pathophysiological function, while excessive adhesion caused by etiological agents is associated with the occurrence and development of many acute and chronic diseases. Cell adhesion inhibitors have been shown to have a potential therapeutic effect on these diseases, therefore, efficient and specific inhibitors against cell adhesion are highly desirable. Here, using lipopolysaccharide-induced human umbilical vein endothelial cells (HUVECs) and calcein-AM-labeled human monocytic cell THP-1, we established a high-throughput screening model for cell adhesion inhibitors with excellent model evaluation parameters. Using the drug repurposing strategy, we screened out lifitegrast, a potent cell adhesion inhibitor, which inhibited cell adhesion between HUVEC and THP-1 cells by directly interrupting the adhesion interaction between HUVEC and THP-1 cells and showed a strong therapeutic effect on the mouse acute liver injury induced by poly (I:C)/D-GalN. Therefore, the screening model is suitable for screening and validating cell adhesion inhibitors, which will promote the research and development of inhibitors for the treatment of diseases caused by excessive cell adhesion.
研究领域:
药理学
·
细胞生物学
·
免疫学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
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