Materials Today Bio
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2025
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IF 10.2
Tingyi Luo,Yujing Tang,Wangcheng Xie,Zhilong Ma,Jian Gong,Yonggui Zhang,Tingsong Yang,Xuyang Jia,Jia Zhou,Zhengyu Hu,Lin Han,Qigang Wang,Zhenshun Song
Severe acute pancreatitis (SAP), a life-threatening inflammatory disease of the pancreas, has a high mortality rate (∼40%). Current therapeutic approaches, including antibiotics, trypsin inhibitors, fasting, rehydration, and even continuous renal replacement therapy, yield limited clinical management efficacy. Abnormally elevated calcium levels and reactive oxygen species (ROS) overproduction by damaged mitochondria are key factors in the inflammatory cascade in SAP. The combination of calcium chelators and cerium-based nanozymes loaded with catalase (MOF808@BA@CAT) was developed to bind intracellular calcium, eliminate excessive ROS, and ameliorate the resulting mitochondrial dysfunction, thereby achieving multiple anti-inflammatory effects on SAP. A single low dose of the nanoplatform (1.5 mg kg −1 ) significantly reduced pancreatic necrosis in SAP rats, effectively ameliorated oxidative stress in the pancreas, improved mitochondrial dysfunction, reduced the proportion of apoptotic cells, and blocked the systemic inflammatory amplification cascade, resulting in the alleviation of systemic inflammation. Moreover, the nanoplatform restored impaired autophagy and inhibited endoplasmic reticulum stress in pancreatic tissue, preserving injured acinar cells. Mechanistically, the administration of the nanoplatform reversed metabolic abnormalities in pancreatic tissue and inhibited the signaling pathways that promote inflammation progression in SAP. This nanoplatform provides a new strategy for SAP treatment, with clinical translation prospects, through ion homeostasis regulation and pancreatic oxidative stress inhibition.
研究领域:
纳米技术
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医学
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药理学
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炎症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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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
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神经科学
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药物递送系统
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传统中药
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中风治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DENTAL MATERIALS
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2024
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IF 4.6
Qingli Zhou,Yuzhu Li,Ting Xiao,Qi Zhong,Leping Wu,Zheng Zhou,Haiming Wong,Quan-Li Li
Objective Extrafibrillar demineralization is considered to be an ideal solution for addressing the durability of resin-dentin bonding interfaces. However, its theoretical basis is contradictory to ionization equilibrium of hydroxyapatite dissolution. In this study, various calcium chelators were selected as dentin conditioners to explore the essence of dentin demineralization with chelators and its effect on resin-dentin adhesion. Methods Polyethyleneimine grafted with EDTA and polyacrylic acid sodium (PAAN 450k ) larger than 40 kDa, as well as PAAN (PAAN 3k ) and EDTA smaller than 6 kDa, were prepared as dentin conditioners. The dentin powder was designed to characterize whether it would demineralize without contact with PAAN 450k . Dentin demineralization effect with four conditioners was evaluated with field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, atomic force microscopy and quantification of hydroxyproline concentration after enzymatic degradation. Micro-tensile bond strength (µTBS) test and failure mode analysis were employed to assess the bonding effect of the four chelators in both wet and dry bonding, with H 3 PO 4 wet bonding serving as the control group. Results Demineralization occurs when PAAN 450k was not in direct contact with the dentin powder. The extrafibrillar demineralization cannot be induced by any chelator regardless of its molecular weight. Complete demineralization including extrafibrillar and intrafibrillar demineralization would occur with sufficient interaction time. Moreover, chelators could not provide a reliable dentin bonding effect under a short interaction time. Significance From the perspective of theory and application, extrafibrillar demineralization is not a reliable strategy, which provides a reminder for exploring new strategies in the future.
研究领域:
牙科材料
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牙科粘接
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材料科学
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生物医学工程
✓ 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）