ACS Applied Nano Materials
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2024
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IF 5.3
Minhua Mo,Jiling Xie,Ziwei Chen,Qiyuan Yang,Xiaowen Hu,Xiaohe Zhou,Janak L. Pathak,Lijing Wang,Chang Liu,Liangjiao Chen
Inadequate vascularization is a major challenge in tissue engineering and can lead to the failure of tissue defect repair. Currently, the use of nanomaterials has emerged as a critical strategy for tissue engineering. Nanoparticles can be utilized as additives in composite materials to enhance the development of bone tissue engineering. Niobium (Nb), a transition metal element with notable biocompatibility, has potential in angiogenesis. However, the effect of Nb nanoparticles (a form of niobium in the nanoparticle state) on endothelial cell behavior remains unclear. This study focused on the effect of Nb nanoparticles on the differentiation of tip cells and its in-depth regulatory mechanism. Our results revealed that Nb nanoparticles promoted angiogenesis at an early stage and increased bone regeneration in calvarial bone defects. In addition, Nb nanoparticles activated tip cell differentiation and thereby promoted cell migration and tube formation. Furthermore, we verified that Nb nanoparticles promoted endothelial tip cell formation by activating YAP. Nb nanoparticles regulates YAP through the newly identified upstream regulatory molecules FOXA1 and PAK4. When FOXA1 or PAK4 was inhibited, YAP expression and tip cell activation were inhibited. Thus, Nb nanoparticles promoted angiogenesis by activating endothelial tip cells, and the FOXA1-PAK4-YAP signaling cascade regulated this process. The insights garnered from this study suggest a strategy for tissue engineering and lay a theoretical foundation for the expanded application of Nb nanoparticles in this field.
研究领域:
组织工程
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纳米技术
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生物医学工程
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Translational Medicine
·
2026
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IF 9.7
Song Yuxuan,Zhang Yingshuang,Gao Yaya,Xu Jingwen,Zang Kai,Zhang Chao,Shi Lei,He Yundong
Background Resistance to androgen receptor signaling inhibitors, including enzalutamide, remains a major obstacle in treating castration-resistant prostate cancer (CRPC). FOXA1, a pioneer transcription factor frequently overexpressed or mutated in prostate cancer, drives disease progression and represents a potential therapeutic target. Methods Through virtual screening, we identified tigecycline, an FDA-approved antibiotic, as a candidate compound that directly targets FOXA1. We assessed its effects on FOXA1 target gene expression and chromatin occupancy using chromatin immunoprecipitation assays in C4‑2 cells. The impact on FOXA1 mutation-driven progression was evaluated using C4‑2 cells stably expressing a FOXA1 point mutant. In vivo efficacy was examined in CRPC xenograft models. Results Tigecycline inhibited FOXA1 target gene expression and reduced FOXA1 chromatin occupancy. In FOXA1-mutant cells, tigecycline repressed mutant-driven gene expression, suppressed AR signaling activity, and decreased PSA levels, reversing the oncogenic effects driven by the mutant. Notably, tigecycline retained efficacy in FOXA1-mutant cell lines, likely through direct binding to FOXA1. In vivo, tigecycline suppressed CRPC tumor growth and reduced tumor PSA levels. Conclusion These findings support tigecycline as a potential therapeutic agent for CRPC by targeting FOXA1.
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DOI
高影响因子
Food & Function
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2025
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IF 5.4
Zhonghua Dong,Xiao Li,Xuan Wang,Jingya Xu,Wei Xu
Background: Diabetic kidney disease (DKD), one of the most common microvascular complications of diabetes mellitus, has been considered the leading cause of end-stage renal disease. Ergosterol is a natural sterol abundant in edible fungi that exhibits pharmacological properties beneficial in the treatment of DKD. However, the precise mechanisms remain elusive. This study aimed to evaluate the therapeutic efficacy of ergosterol in DKD and to delineate the underlying mechanisms. Methods: Transcriptome microarray sequencing data from DKD patients retrieved from the public GEO database, as well as data from mouse DKD models, were analyzed to identify differentially expressed genes. Db/db mouse, high-glucose-induced HK-2 cells and conditioned THP-1 cells were employed to evaluate the impact of ergosterol on renal function, lipid metabolism and macrophage phenotypic transformation. Results: Transcriptional profiling of DKD kidneys revealed alterations in fatty acid metabolism, which were corroborated in db/db mice. Ergosterol significantly improved renal function, reduced lipid accumulation, and mitigated inflammation. CPT1A, a key modulator of fatty acid metabolism, was identified as a target. The inhibition of CPT1A in renal tubular epithelial cells led to impaired fatty acid oxidation and lipid accumulation. Excessive renal lipids further stimulated macrophages to transform into pro-inflammatory phenotypes, leading to renal inflammation infiltration and exacerbating kidney damage. Ergosterol upregulated CPT1A expression through transcriptional regulation of FOXA1, thereby reducing lipid accumulation and subsequent renal inflammation. Conclusion: Ergosterol enhances renal fatty acid oxidation via the FOXA1/CPT1A pathway, reducing renal lipid accumulation and inflammation, potentially delaying DKD progression. This study elucidates the therapeutic potential of ergosterol in DKD and provides new insights into the treatment of DKD.
研究领域:
药理学
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分子生物学
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肾脏病学
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代谢性疾病
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免疫学
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营养科学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）