JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Lianxin Li,Yu Xiong,Yuewen Zhang,Yujiao Yan,Ruixin Zhao,Fengmei Yang,Meng Xie
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of β-amyloid protein (Aβ), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu 2+ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aβ deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu 2+ -induced Aβ monomers aggregation, eliminate the deposition of Aβ plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu 2+ -induced Aβ monomers aggregation, photothermally depolymerizing Aβ fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD.
研究领域:
神经科学
·
纳米技术
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Shengnuo Fan,Yuqiu Zheng,Xuan Liu,Wenli Fang,Xiaoyu Chen,Wang Liao,Xiuna Jing,Ming Lei,Enxiang Tao,Qiulan Ma,Xingmei Zhang,Rui Guo,Jun Liu
Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.
研究领域:
神经科学
·
药学
·
纳米技术
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2021
·Vol. 7
·期 1
·1-13
·
IF 5.241
Yang Xiu,Li Xu,Liu Le,Chen Yuan-Hao,You Yue,Gao Yin,Liu Yue-Ying,Yang Li,Tong Kun,Chen Di-Shi,Hao Jing-Ru,Sun Nan,Zhao Zi-Ming,Gao Can
Alzheimer’s disease (AD) is characterized by aberrant accumulation of extracellular β-amyloid (Aβ) peptides in the brain. Soluble Aβ oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both Aβ oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the Aβ burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture Aβ oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered Aβ1-42 aggregation and disaggregated Aβ1-42 assembly due to multivalent PA-Aβ. Pep63 effectively inhibited the binding between EphB2 and Aβ oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 12
·1-11
·
IF 5.3
Tan Suhui,Tan Mengyuan,Zhang Tao,Gao Lu,Li Yi,Xu Xuechao,Yang Zhen-quan
A multienzyme-like L-argininemodified CeO 2 (Arg-CeO 2 ) nanozyme was prepared for accurate total antioxidant capacity (TAC) determination of Ganoderma sichuanense ( G. sichuanense ). It exhibits oxidase-like and peroxidase-like activities catalyzing the generation of superoxide anion free radicals and hydroxyl radicals, accelerating 3, 3′, 5, 5′-tetramethylbenzidine (TMB) chromogenic reaction. Antioxidants can effectively eliminate the generated free radicals, inhibiting the TMB chromogenic reaction. Hence, TAC can be assessed by Arg-CeO 2 catalyzed TMB chromogenic reaction using ascorbic acid (AA) as a reference substance. TAC of G. sichuanense extracted using different solvents was determined, indicating the highest TAC observed in the G. sichuanense extracted by the mixture solvent (deionized water/ethanol/ethyl acetate = 1 : 1 : 1). A visual assessment platform based on Arg-CeO 2 hydrogel nanozyme utilizing a self-programmed smartphone app and a self-designed 3D printed device is established. TAC using AA as a reference substance (3.33 ~ 83.33 µM) can be detected with a detection limit as low as 0.58 µM. The platform can realize one-step quantitative determination of TAC in G. sichuanens e within 40 min. The proposed visual assessment platform presented exhibits promising application prospects in the field of TAC assessment in food. Graphical
研究领域:
食品科学
·
生物化学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 27
·13129-13136
·
IF 3.925
Ping Zhang,Xianliang Li,Yan Xu
Excessive use of tetracycline (TC) exacerbates environmental pollution and seriously threatens human health. Therefore, it is of great significance to explore an effective approach for detecting TC. In this work, a water-stable and ratiometric luminescent sensor based on a dual-emitting Eu-based metal–organic framework (Eu-TCPE, H4TCPE = tetrakis(4-carboxyphenyl)ethylene) was established through a solvothermal method. Benefiting from the luminescence quenching behavior of H4TCPE linkers through the inner filter effect (IFE) and the enhanced fluorescence emission of Eu3+via the antenna effect, supported by the results of UV-vis absorption spectra and density functional theory (DFT) calculations, the Eu-TCPE sensor exhibited a fast and selective response towards TC detection with a low detection limit of 14 nM in a linear range of 0–50 µM. Application of the Eu-TCPE sensor in real samples of tap water and milk was also investigated. Furthermore, a test-strip-based sensor with the Eu-TCPE probe fixed on the surface was developed for the real-time selective detection of TC in aqueous solution, and the fluorescence color changes of the test strip under UV-light excitation can be captured using the portable online analyzer of a smartphone-color detector App, which showed a handheld platform for the rapid and visual detection of TC in practical applications.
研究领域:
环境科学
·
分析化学
·
材料科学
·
生物技术
✓ 已验证
DOI
高影响因子
Nanoscale
·
2024
·Vol. 16
·期 9
·4811-4825
·
IF 5.8
Menghan Guo,Wenqing Wang,Bin Zhai,Jingtao Li,Liran Zhang,Jingchun Li,Kexin Luo,Rui Wang
Flammability feature of textiles is a big underlying risk causing fire disasters. The fabrication of reliable fire resistant and quick fire warning fabrics is imperative but challenging. Herein, three types of early fire-warning polyester fabrics, namely, FPP@AM-X, FPP@PM-X and FPP@AX-M1, with good flame retardant and piezoresistive sensing performance were developed by fabricating polyethyleneimine (PEI), ammonium polyphosphate (APP), phytic acid (PA) and MXenes onto phosphorus-containing flame retardant polyethylene terephthalate (FRPET) via polydopamine (PDA) mediated layer-by-layer self-assembly. Owing to the improved thermoelectric properties of MXenes, FPP@A5-M1 exhibited a maximum thermoelectric voltage of 0.59 mV at a temperature difference of 130 °C and can provide an ideal cyclic early fire warning response within 4 s. In addition, due to the synergistic flame retardant effect of MXenes and APP in the coating layer, FPP@A5-M1 could be self-extinguished within 2 s after ignition and the value of peak heat release ratio and total smoke production decreased by 41.9% and 30.4%, respectively. Besides, the MXene-based hybrid coated fabric can detect the movement of human fingers and elbows, illustrating its potential application in piezoresistive tension sensing. This work provides a new route to designing and developing multi-functional and smart fire protection fabrics.
研究领域:
材料科学
·
纺织工程
·
消防安全
·
智能纺织品
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Wen-Qiao Qiu,Rong Pan,Yong Tang,Xiao-Gang Zhou,Jian-Ming Wu,Lu Yu,Betty Yuen-Kwan Law,Wei Ai,Chong-Lin Yu,Da-Lian Qin,An-Guo Wu
Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSP dose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSP could significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together, LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.
研究领域:
神经科学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Caihua Ye,Meng Cheng,Lin Ma,Tianzhu Zhang,Zuhao Sun,Chunshui Yu,Junping Wang,Yan Dou
Prevention of Alzheimer’s disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aβ deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
研究领域:
神经科学
·
药理学
·
神经炎症
·
药物递送系统
·
阿尔茨海默病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chunlan Tang,Zhiling Fang,Donghui Chu,Lulu Zhang,Yuqing Tang,Jinyue Zhou,Rui Fang,Jiaming Ying,Fang Wang,Yuping Zhou,Chunshuang Xu,Qinwen Wang
Alzheimer’s disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo . Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3β, ESR1, and AR targets based on the anti-β-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer’s disease pathway, APP and GSK3β, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3β protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.
研究领域:
神经学
·
药理学
·
中医药
·
网络药理学
·
药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2021
·
IF 7.376
Wen-Qiao Qiu,Wei Ai,Feng-Dan Zhu,Yue Zhang,Min-Song Guo,Betty Yuen-Kwan Law,Jian-Ming Wu,Vincent Kam-Wai Wong,Yong Tang,Lu Yu,Qi Chen,Chong-Lin Yu,Jian Liu,Da-Lian Qin,Xiao-Gang Zhou,An-Guo Wu
Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Jing Sun,Chunfang Wei,Yanan Liu,Wenjie Xie,Mengmeng Xu,Hui Zhou,Jie Liu
Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis. Controlled release , target ability, and multi-channel synergistic treatment are key factors associated with the success of AD drugs. Herein, we report a novel mesoporous nano-selenium (MSe) release delivery system (MSe-Res/Fc-β-CD/Bor) based on the borneol (Bor) target, β-cyclodextrin nanovalves (Fc-β-CD) with loaded resveratrol (Res). Previous experiments have shown that MSe-Res/Fc-β-CD/Bor first releases Bor by interacting with blood or intracellular esterases , allowing the nanosystem to pass through the blood-brain barrier (BBB). Subsequently, the Fc-β-CD is opened by the redox (H 2 O 2 ) response to the release of Res at the lesion site. We demonstrated that MSe-Res/Fc-β-CD/Bor inhibited aggregation of β-amyloid proteins (Aβ), mitigated oxidative stress , and suppressed tau hyperphosphorylation , while protecting nerve cells and successfully improving memory impairment in APP/PS1 mice. Interestingly, compared with rivastigmine (Riv) positive drugs alone, the MSe/Fc-β-CD/Bor loaded with Riv had a better pharmacokinetic index. These results indicate that MSe-Res/Fc-β-CD/Bor could be a prospective drug for treating AD.
研究领域:
神经学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2018
·
IF 4.936
Pan Liu,Xiao Chen,Haizhe Zhou,Liqun Wang,Zaijun Zhang,Xiaohu Ren,Feiqi Zhu,Yi Guo,Xinfeng Huang,Jianjun Liu,Peter S. Spencer,Xifei Yang
Alzheimer’s disease (AD), the most common neurodegenerative disease, has no effective treatment. Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, reportedly has neuroprotective effects in cerebral ischemia. Here, we investigated the effects of DAU on N2a cells stably transfected with Swedish mutant amyloid precursor protein (N2a/APP), an AD-like cell model. ELISA and Western blot analysis revealed that DAU inhibited APP processing and reduced Aβ accumulation. In addition, DAU ameliorated tau hyperphosphorylation via PP2A, p35/25, and CDK5 pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by DAU was also validated in HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis revealed 85 differentially expressed proteins in the lysates between the wild-type N2a cells (N2a/WT) and the N2a/APP cells in the presence or absence of DAU; these were classified into 6 main categories according to their functions: endoplasmic reticulum (ER) stress-associated proteins, oxidative stress-associated proteins, cytoskeleton proteins, molecular chaperones, mitochondrial respiration and metabolism-related proteins, and signaling proteins. Taken together, we demonstrated that DAU treatment reduces AD-like pathology, thereby suggesting that DAU has potential therapeutic utility in AD.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）