CURRENT MEDICINAL CHEMISTRY
·
2023
·
IF 4.1
Xu Cong,Zhang Cheng,Ganesan Kumar,Qui Chen,Tang Hailin,Gao Fei,Liu Qingqing,Wu Jianming,Sui Yue,Li Peng,Zhang Jinming,Chen Jianping
Introduction: Triple-negative breast cancer (TNBC), an aggressive type of
breast cancer, remains difficult to treat. Isoliquiritigenin (ISL) is a bioactive compound
that is insoluble in water and exhibits significant anti-TNBC activity. Method: We previously
prepared oral aqueous ISL@ZLH NPs; however, they were less stable in a freezing
environment. Hence, the present study aimed to improve the stability of ISL@ZLH
NPs using cryoprotectants that can withstand long storage times and are effective in TNBC
treatment by creating an efficient oral drug delivery system. Freeze-dried ISL@ZLH
NP powder was prepared by solvent evaporation, followed by the addition of trehalose
and sucrose. The freeze-dried ISL@ZLH NP pow was optimized and characterized. The
anti-TNBC efficacy and pharmacokinetics of the ISL@ZLH NP-pow were examined in
plasma and organs, compared with those of aqueous ISL@ZLH NPs. Result: The ideal
particle size of the ISL@ZLH NP pow was 118 nm, which was not filtered out by the
glomerulus and allowed the drug to be delivered to the lesions more effectively. Cellular
uptake and biodistribution of the ISL@ZLH NP-pow in vivo and in vitro showed prolonged
storage in the organs. In addition, cryopreserved ISL@ZLH NP-treated tumors
showed significant anti-proliferative and anti-migratory effects through the downregulation
of the PI3K-Akt-mToR and MMP2/9 signaling pathways. Conclusion: These results
suggest that oral ingestion of cryopreserved ISL@ZLH NP has the potential for longterm
storage and can be employed as a clinical therapeutic approach to treat TNBC.
研究领域:
肿瘤学
·
药剂学
·
纳米技术
·
药物递送系统
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
·
2024
·
IF 3.7
Jingying Qin,Cheli Wang,Xiaoying Zhou
Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis/apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depended on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yahong Li,Junjin Zhu,Xin Zhang,Yuanyuan Li,Shu Zhang,Linxin Yang,Ruyi Li,Qianbing Wan,Xibo Pei,Junyu Chen,Jian Wang
It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the half-life of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis–osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO@ZIF-8. Additionally, due to the sustained release of DFO and Zn2+, DFO@ZIF-8 NPs were able to promote angiogenesis in human umbilical vein endothelial cells (HUVECs) culture and osteogenesis in bone marrow stem cells (BMSCs) in vitro. Furthermore, the DFO@ZIF-8 NPs promoted vascularization by enhancing the expression of type H vessels and a vascular network. The DFO@ZIF-8 NPs promoted bone regeneration in vivo by increasing the expression of OCN and BMP-2. RNA sequencing analysis revealed that the PI3K-AKT-MMP-2/9 and HIF-1α pathways were upregulated by DFO@ZIF-8 NPs in HUVECs, ultimately leading to the formation of new blood vessels. In addition, the mechanism by which DFO@ZIF-8 NPs promoted bone regeneration was potentially related to the synergistic effect of angiogenesis–osteogenesis coupling and Zn2+-mediation of the MAPK pathway. Taken together, DFO@ZIF-8 NPs, which were demonstrated to have low cytotoxicity and excellent coupling of angiogenesis and osteogenesis, represent a promising strategy for the reconstruction of critical-sized bone defects.
研究领域:
骨组织工程
·
纳米技术
·
药学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yanan Wang,Xutao Ma,Xinyuan Wang,Liru Liu,Xue Zhang,Qiuyue Wang,Yingfei Zhu,Huanhua Xu,Liangmin Yu,Zhiyu He
The scarcity of effective neuroprotective agents and the presence of blood-brain barrier (BBB)-mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS-responsive borneol-based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain-targeting ligand, inner hydrophobic core for efficient drug loading of membrane-permeable calcium chelator BAPTA-AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA-AM: 400 µg·kg −1 ) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl-2/Bax/Cyto-C/Caspase-3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over-activation, reprogramming microglia polarization toward an anti-inflammatory phenotype, and blocking NF-κB/TNF- α /IL-6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple-stage sequential treatment strategy for clinical CIS.
研究领域:
药学
·
神经科学
·
药物递送系统
·
传统中药
·
中风治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2023
·Vol. 10
·期 12
·3389-3400
·
IF 7.3
Shuoli Ma,Wen-Xiong Wang
Marine hydrosphere is in grave danger if extreme weather conditions, such as high temperatures and heat waves, become the norm. The functional characteristics of nano Zn oxides (nZnO) might provide a “booster substance” that helps marine species to endure environmental stress. In the present study, physiological indicators and simulated severe environments were used to evaluate the antioxidative ability of nZnO in marine rabbitfish Siganus fuscescens, with an aim to help them resist extreme environmental stress. Rabbitfish were exposed to different diets with ZnSO4 and nZnO at the optimum requirement level (Zn content of 62.5 μg g−1), and then challenged with a low dissolved oxygen concentration and higher temperature. We demonstrated that dietary nZnO promoted the anti-oxidation defense system of the rabbitfish by improving the activities of the antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio without tissue damage. Compound stressors reduced the median survival duration of the rabbitfish from 4.25 h to 2.5 h (dietary exposure) and 9 h to 5.75 h (dietary nZnO exposure) compared to single environmental stress. nZnO downregulated the HIF gene expression and increased the prolyl hydroxylase (PHD) activity in the liver of the rabbitfish. After 10 h of extreme environmental exposure, the gene expression results indicated that nZnO inhibited the NF-κB/IL-1β/IL-6 pathway and TNF-α/Bcl-2/Bax/caspase 9 pathway and activated the akt/mTOR/elovl5 and elovl8 pathway of the rabbitfish to maintain the resilience of the fish under the extreme environment. These results strongly suggested that nZnO may improve the anti-oxidation ability of fish to resist extreme environments.
研究领域:
海洋生物学
·
环境科学
·
水产养殖
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）