Oncotarget
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2016
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IF 5.008
Qiao Tang,Yajun Liu,Tao Li,Xiang Yang,Guirong Zheng,Hongning Chen,Lee Jia,Jingwei Shao
Metastasis currently remains the predominant cause of breast carcinoma treatment failure. The effective targeting of metastasis-related-pathways in cancer holds promise for a new generation of therapeutics. In this study, we developed an novel Asp-UA conjugate, which was composed of classical “old drug” aspirin and low toxicity natural product ursolic acid for targeting breast cancer metastasis. Our results showed that Asp-UA could attenuate the adhesion, migration and invasion of breast cancer MCF-7 and MDA-MB-231 cells in a more safe and effective manner in vitro . Molecular and cellular study demonstrated that Asp-UA significantly down-regulated the expression of cell adhesion and invasion molecules including integrin α6β1, CD44, MMP-2, MMP-9, COX-2, EGFR and ERK proteins, and up-regulated the epithelial markers “E-cadherin” and “β-catenin”, and PTEN proteins. Furthermore, Asp-UA (80 mg/kg) reduced lung metastasis in a 4T1 murine breast cancer metastasis model more efficiently, which was associated with a decrease in the expression of CD44. More importantly, we did not detect side effects with Asp-UA in mice such as weight loss and main viscera tissues toxicity. Overall, our research suggested that co-drug Asp-UA possessed potential metastasis chemoprevention abilities via influencing EMT and EGFR-mediated pathways and could be a more promising drug candidate for the prevention and/or treatment of breast cancer metastasis.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL
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2024
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IF 45.5
Feng Lin,Shenyi Yin,Zijian Zhang,Ying Yu,Haoming Fang,Zhen Liang,Rujie Zhu,Haitao Zhou,Jianjie Li,Kunxia Cao,Weiming Guo,Shan Qin,Yuxuan Zhang,Chenghao Lu,Han Li,Shibo Liu,Heng Zhang,Buqing Ye,Jian Lin,Yan Li,Xiaozheng Kang,Jianzhong Jeff Xi,Peng R. Chen
Although immunotherapy has revolutionized cancer treatment, its efficacy is affected by multiple factors, particularly those derived from the complexity and heterogeneity of the tumor-immune microenvironment (TIME). Strategies that simultaneously and synergistically engage multiple immune cells in TIME remain highly desirable but challenging. Herein, we report a multimodal and programmable platform that enables the integration of multiple therapeutic modules into single agents for tumor-targeted co-engagement of multiple immune cells within TIME. We developed the triple orthogonal linker (T-Linker) technology to integrate various therapeutic small molecules and biomolecules as multimodal targeting chimeras (Multi-TACs). The EGFR-CD3-PDL1 Multi-TAC facilitated T-dendritic cell co-engagement to target solid tumors with excellent efficacy, as demonstrated in vitro , in several humanized mouse models and in patient-derived tumor models. Furthermore, Multi-TACs were constructed to coordinate T cells with other immune cell types. The highly modular and programmable feature of our Multi-TACs may find broad applications in immunotherapy and beyond.
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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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Lianxue Zhang,Yun Teng,Hai Yang,Jianxiang Huang,Zhaoqi Shi,Cenhao Wu,Zaixing Yang,Liquan Huang,Jun Zou,Ruhong Zhou
Chordoma presents a formidable therapeutic challenge due to its distinct anatomical location, thus complicating its complete surgical resection coupled with marked resistance to both radiotherapy and chemotherapy. Currently, effective systemic therapies remain unavailable, contributing to a poor prognosis for patients. To address this critical unmet need, we have developed a targeted drug delivery system tailored to the tumor biology of chordoma. This system encapsulates the CDK7 inhibitor THZ1 within nanoparticles featuring diselenide bonds as dual-responsive release triggers. Upon exposure to low-dose X-ray irradiation (e.g., 2 Gy) and to the elevated reactive oxygen species (ROS) level in the tumor microenvironment, these diselenide bonds are cleaved and transformed into selenic acid (RSeOOH), which subsequently initiates rapid carrier disassembly and drug release. The synergy between RSeOOH and THZ1 enhances radiotherapy efficacy by modulating p53 signaling, inducing apoptosis, and promoting G2/M phase cell cycle arrest in U-CH1 cells, thereby overcoming the radiotherapy resistance commonly seen in chordoma. To further improve tumor-specificity, we functionalize the carrier with the EGFR-targeting GE11 peptide, which drives selective drug accumulation at tumor sites. In murine models, this delivery system has demonstrated substantial efficacy in combination with radiochemotherapy and yet produces minimal toxicity. Molecular dynamics simulations have further elucidated carrier self-assembly mechanisms, guiding the rational design of this nanoplatform.
研究领域:
纳米医学
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肿瘤学
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放射治疗学
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药理学
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生物化学
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生物物理学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Qiao Zhang,Jinlin Chen,Tianyu Zhang,Dan Liu,Xirui Long,Jiehua Li,Lu Jiang,Yanchao Wang,Hong Tan
In the field of oral and maxillofacial surgery, extensive oral soft-tissue injuries occur repeatedly in clinical practice; however, effective restorative materials are lacking. In this study, a biodegradable waterborne polyurethane patch featuring a mucosa bionic bilayer structure is presented. This patch consists of a porous scaffold layer that faces the lesion, incorporating a polydopamine coating to achieve sustained release of epidermal growth factors (EGFs) for mucosal defect reconstruction. Additionally, there is a dense barrier layer toward the oral cavity loaded with silver nanoparticles, which prevents bacteria from entering the wound and simultaneously acts as a physical barrier. This patch can sustainably release EGF in vitro for 2 weeks, thereby facilitating the proliferation and migration of HaCaT and L929 cells, while effectively killing common oral cavity bacteria. In a rabbit buccal mucosal full-thickness defect model, the patch demonstrates better efficacy than the clinical benchmark, decellularized extracellular matrix (dECM). It effectively reduces wound inflammation and significantly upregulates gene expression associated with epithelialization by activating the EGF/epidermal growth factor receptor (EGFR) pathway. These mechanisms promote the proliferation, differentiation, and migration of epithelial/keratinocyte cells, ultimately expediting mucosal defect healing and wound closure.
研究领域:
口腔颌面外科
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组织工程
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生物医学材料
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2025
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IF 5.9
Ruoxin Chen,Jiahao Ren,Zhenlong Zhou,Wenjun Zhang,Jianyu Su
Gentiana rigescens Franch. extract have demonstrated various important bioactivities, however, their potential against photoaging has yet to be evaluated. This study explored the anti-photoaging effects of Gentiana rigescens Franch. root extract (GRFR) and stem (GRFS), along with their underlying mechanisms and bioactive components, using the UVB-induced zebrafish model. GRFS demonstrated superior anti-photoaging efficacy compared to GRFR. GRFS significantly alleviated UVB-induced tail fin damage, increasing the relative tail fin area from 31.23% to 80.92% (at 1mg/mL), and reducing ROS levels from 244.80% to 150.95%. It also inhibited lipid peroxidation, lowering malondialdehyde (MDA) levels from 202.87 nmol/g to 142.83 nmol/g. Furthermore, GRFS enhanced antioxidant enzyme activities, increasing superoxide dismutase (SOD) from 80.94 U/g to 104.06 U/g. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) indicated substantial distinctions in the composition and content of major constituents between GRFR and GFRS, which may explain the differences in their anti-photoaging activities. And then network pharmacology was used to investigate possible mechanisms of GFRS, which identified five potential targets including CTNNB1, ESR1, AKT1, JUN and EGFR, as well as three key active compounds including aspartyl-phenylalanine (Asp-Phe), N-acetyl-L-phenylalanine (N-Acetyl-L-Phe), and phenylalanyl-tyrosine (Phe-Tyr). Finally, the molecular docking revealed that Phe-Tyr exhibited the strongest binding affinity for AKT1 (-8.86 kcal/mol), indicating that it may be the most potent anti-photoaging compound in GFRS. These findings suggest that G . rigescens , with its potent anti-photoaging properties, offers superior protection against UVB-induced photoaging and holds promise as a natural therapeutic agent.
研究领域:
药理学
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植物学
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皮肤科学
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生物化学
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计算生物学
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天然产物研究
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
American Journal of Cancer Research
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2024
·
IF 3.6
Haiyue Zhu,Yuxin Bao,Xuanqi Dou,Xiaofeng Zuo,Junhong Ye,Haiyu Ma,Youquan Bu,Yitao Wang,Jiang Zhu
Head and neck squamous cell carcinoma (HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Our studies have revealed that KIF2C plays a crucial role in tumor proliferation and metastasis in HNSCC. The results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels and is closely associated with lymph node metastasis. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicate that the differentially expressed genes are enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Moreover, the established protein-protein interaction network identifies KIF2C as a potential hub gene in HNSCC. Knockdown of KIF2C has been demonstrated to significantly reduce cell migration and invasion ability, leading to cell cycle arrest, a high proportion of abnormal cell apoptosis, and cell chromosome division mismatches in the HNSCC cell line. Downstream genes such as PDGFA, EGFR, TP63, SNAI2, KRT5, and KRT14 were found to be down-regulated, and multiple critical pathways, including mTOR, ERK, and PI3K-AKT pathways, were inactivated as a result of KIF2C knockdown. These findings provide strong evidence for the crucial role of KIF2C in HNSCC and suggest that targeting KIF2C may be a promising therapeutic strategy for this disease. Knockdown of KIF2C has been shown to significantly inhibit tumor proliferation in nude mice, demonstrating the potential therapeutic role of KIF2C in HNSCC treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
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2023
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IF 4
Lingling Song,Jian Xu,Yanqiong Shi,Hemiao Zhao,Min Zhang,Yuefei Wang,Ying Cui,Xin Chai
Febrile seizures (FS) are the most common type of seizures for children. As a commonly used representative cold formula for resuscitation, Zixue Powder (ZP) has shown great efficacy for the treatment of FS in clinic, while its active ingredients and underlying mechanism remain largely unclear. This study aimed to preliminarily elucidate the material basis of ZP and the potential mechanism for the treatment of FS through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and molecular docking. UPLC-Q-TOF-MS was firstly applied to characterize the ingredients in ZP, followed by network pharmacology to explore the potential bioactive ingredients and pathways of ZP against FS. Furthermore, molecular docking technique was employed to verify the binding affinity between the screened active ingredients and targets. As a result, 75 ingredients were identified, containing flavonoids, chromogenic ketones, triterpenes and their saponins, organic acids, etc. Through the current study, we focused on 13 potential active ingredients and 14 key potential anti-FS targets of ZP, such as IL6, STAT3, TNF, and MMP9. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that inflammatory response, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, and neuroactive ligand-receptor interaction were the main anti-FS signaling pathways. Licochalcones A and B, 26-deoxycimicifugoside, and hederagenin were screened as the main potential active ingredients by molecular docking. In conclusion, this study provides an effective in-depth investigation of the chemical composition, potential bioactive components, and possible anti-FS mechanism of ZP, which lays the foundation for pharmacodynamic studies and clinical applications of ZP.
研究领域:
药理学
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分析化学
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神经科学
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中医中药
✓ 已验证
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Shuangliu Chen,Yalan Pan,Yang Guo,Xiaoxian Sun,Xue Bai,Mengmin Liu,Lining Wang,Jiřimutu Xiao,Cheng Chen,Yong Ma
This study utilized bioinformatics and data mining techniques to explore the molecular mechanism of curcumin in treating osteoporosis (OP) through the lens of ferroptosis, thereby identifying novel therapeutic targets. The datasets GSE35958, GSE35956, GSE7429, and GSE7158 were obtained from the Gene Expression Omnibus (GEO) database. GSE35958 and GSE35956 were employed as training sets for data integration, while GSE7429 and GSE7158 served as independent validation sets. Through retrieval from the FerrDb database, iron death-related genes (FRGs) were identified, and the differentially expressed genes (DEGs) were intersected to obtain differentially expressed FRGs (DEFRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, followed by the construction of a Protein-Protein Interaction (PPI) network to identify Hub genes. The DGIdb database was utilized to predict candidate drugs associated with the Hub genes, and molecular docking and in vitro experiments confirmed that curcumin targets the Hub genes EGFR and PTGS2.Through in vitro testing of curcumin on BMSC cells, researchers examined cell vitality, iron death, osteogenic differentiation, mineralization, and the impact on EGFR and PTGS2 levels. The analysis yielded 2212 DEGs, 484 FRGs, with 45 FDEGs at the intersection. GO analysis revealed involvement in regulating mitochondrial proteins, amino acid transport across plasma membranes, and protein ubiquitination. KEGG pathway analysis indicated associations with iron death, FoxO signaling, mTOR signaling, cell aging, osteoclast differentiation, and GSH metabolism. Utilizing the MCC algorithm, five Hub genes were identified: MAPK3, PTGS2, TGFB1, CYBB, and EGFR, showing diagnostic potential for iron death. Curcumin displayed affinity for EGFR and PTGS2, mitigating iron-induced effects on BMSCs such as increased reactive oxygen species, Fe3+ levels, and decreased mitochondrial membrane potential. Furthermore, curcumin reversed these effects, suggesting EGFR and PTGS2 as targets for curcumin to inhibit BMSC ferroptosis and potentially delay osteoporosis development. Maintaining iron homeostasis and targeting BMSC ferroptosis could offer therapeutic avenues for iron overload-induced osteoporosis.
研究领域:
生物信息学
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药理学
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分子生物学
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医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
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