CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jie Zhang,Jiahui Shi,Qiubo Yang,Haogang Guo,Lingfeng Guo,Guoliang Zhou,Yinyi Liu,Xiaolei Wang,Xian Hao,Yifei Yang
Parkinson's disease (PD), a neurodegenerative disorder characterized by the depletion of dopaminergic neurons, has conventionally been managed through pharmacological intervention and deep brain stimulation (DBS) surgery. However, drug resistance and the risks of surgical implantation have hindered the effective of current treatment. Herein, we endeavor to engineer a wireless, non-invasive nanoplatform for electrostimulation-enhanced drug therapy, termed BCFO@LCM. This innovative platform integrates magnetoelectric nanomaterials (BaTiO 3 -CoFe 2 O 4 ) encapsulated within BV2 cell membranes (CM), enabling traversal of the blood-brain barrier (BBB) and dual-targeting of the PD microenvironment through magnetic and membrane fusion mechanisms. When exposed to an external magnetic field, this system facilitates the controlled release of the therapeutic agent L-DOPA for pharmacotherapy, concurrently generating electrical signals via the magnetoelectric nanomaterials to effectuate neuromodulation. Our findings reveal that BCFO@LCM markedly ameliorates dyskinesia in PD model mice, diminishes the attrition of dopaminergic neurons in the substantia nigra and striatum, augments tyrosine hydroxylase levels, and ultimately reverses the damage to dopaminergic neurons. Furthermore, the non-invasive electrical stimulation enhances neuronal activity within deep brain tissues and fosters the regeneration and differentiation of neurons.
研究领域:
神经科学
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纳米医学
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生物医学工程
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再生医学
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神经退行性疾病
✓ 已验证
产品关联
DOI
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·
IF 5.5
Xiaolu Hu,Lan Yu,Yatong Li,Xiaoxi Li,Yimeng Zhao,Lijuan Xiong,Jiaxuan Ai,Qijun Chen,Xing Wang,Xiaoqing Chen,Yinying Ba,Yaonan Wang,Xia Wu
Aim Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). Methods Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis . Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis -transplanted rats. Results We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. Conclusion Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.
研究领域:
神经科学
·
药理学
·
微生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Chong Li,Wei Xu,Lei Li,Yonghui Zhou,Gang Yao,Guang Chen,Lei Xu,Ning Yang,Zhanjun Yan,Chen Zhu,Shiyuan Fang,Yusen Qiao,Jiaxiang Bai,Meng Li
Osteoporotic fractures are characterized by abnormal inflammation, deterioration of the bone microenvironment, weakened mechanical properties, and difficulties in osteogenic differentiation. The chronic inflammatory state characterized by aging macrophages leads to delayed or non-healing of the fracture or even the formation of bone defects. The current bottleneck in clinical treatment is to achieve strong fixation of the comminuted bone fragments and effective regulation of the complex microenvironment of aging macrophages. Inspired by cement and gravel in concrete infrastructure, a biomimetic bone glue with poly(lactic-co-glycolic acid) microspheres is developed and levodopa/oxidized chitosan hydrogel stabilized on an organic-inorganic framework of nanohydroxyapatite, named DOPM. DOPM is characterized via morphological and mechanical characterization techniques, in vitro experiments with bone marrow mesenchymal stromal cells, and in vivo experiments with an aged SD rat model exhibiting osteoporotic bone defects. DOPM exhibited excellent adhesion properties, good biocompatibility, and significant osteogenic differentiation. Transcriptomic analysis revealed that DOPM improved the inflammatory microenvironment by inhibiting the NF-κB signaling pathway and promoting aging macrophage polarization toward M2 macrophages, thus significantly accelerating bone defect repair and regeneration. This biomimetic bone glue, which enhances osteointegration and reestablishes the homeostasis of aging macrophages, has potential applications in the treatment of osteoporotic bone defects.
研究领域:
生物材料
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组织工程
·
再生医学
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骨科
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炎症生物学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Suyun Rao,Ke Xiao,Xuhui Chen,Xufang Sun
Diabetic retinopathy (DR) is a major cause of vision impairment, with diabetic retinal neurodegeneration (DRN) identified as an early pathological feature. Although dopamine (DA) has demonstrated protective effects in various neurodegenerative diseases, its role in DRN is inadequately understood. This study provides evidence that DA can alleviate DRN impairment and elucidates the underlying mechanisms. Diabetes was induced in C57BL/6 mice through a single large dose injection of streptozotocin, and the dopamine precursor l-DOPA was administered via intraperitoneal injection daily for 2 weeks to therapeutically supplement dopamine levels. The results indicated that l-DOPA treatment significantly restored retinal thickness, enhanced the amplitude of oscillatory potentials, and alleviated retinal glial cell activation compared to diabetic mice. In vitro, DA treatment of SH-SY5Y cells under high-glucose stress led to a significant increase in superoxide dismutase activity, with a reduction in malondialdehyde levels, lipid peroxide, and iron ion concentration. Additionally, the expression of GPX4, SLC7A11, ferritin, Nrf2, and HO-1 proteins was upregulated, while the expression of NCOA4 was downregulated. Importantly, the protective effects of DA were significantly attenuated by the Nrf2 inhibitor ML385, confirming the involvement of the Nrf2/HO-1 pathway in DA’s protective mechanism. These findings suggest that DA alleviates oxidative stress, reduces ferroptosis, and improves the retinal function in DRN through the activation of the Nrf2/HO-1 pathway, indicating that DA may represent a novel therapeutic strategy for treating DRN.
研究领域:
神经科学
·
眼科学
·
分子生物学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 2
·e70250
·
IF 5
Yuewei Bi,Pengfei Wang,Min Li,Zhuyong Wang,Siyuan Lv,Yong Yang,Wangming Zhang
Aims Dopamine replacement therapy is the backbone of Parkinson's disease (PD) treatment. However, long-term levodopa ( L -DOPA) administration can lead to the severely disabling motor complication L-DOPA-induced dyskinesia (LID), for which standard, effective therapy is currently lacking. This study was conducted to characterize the distinct neural electrophysiological patterns involved in the progression of PD and to examine the efficacy of tetrabenazine, a vesicular monoamine transporter-2 inhibitor, in alleviating dyskinesia and its underlying electrophysiological mechanism. Methods Electrophysiological analysis was performed to obtain power spectrum density and functional connectivity information from local field potential (LFP) data recorded from the primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states in PD model rats. Behavioral tests and abnormal involuntary movements (AIMs) scoring were conducted to confirm PD model establishment and assess LID severity. Results Increased beta oscillations and abnormally strengthened beta causality in the M1 → DLS direction and exaggerated beta-band M1–DLS functional connectivity were observed in the PD state. L -DOPA administration suppressed beta activity and augmented gamma power in the M1 and DLS, with increased gamma causality in the M1 → DLS direction and beta causality in the DLS → M1 direction, as well as elevated gamma-band M1–DLS functional connectivity. Tetrabenazine strongly ameliorated dyskinetic manifestations. It suppressed gamma power in the M1 and DLS, reduced gamma causality and increased beta causality in the M1 → DLS direction, reduced beta causality in the DLS → M1 direction, and reduced gamma-band M1–DLS functional connectivity. Conclusion Tetrabenazine abrogated aberrant gamma activity to improve LID symptoms, which provides compelling evidence for its future clinical application in LID therapy.
研究领域:
神经科学
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药理学
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电生理学
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神经病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
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IF 4.787
Yanping Li,Yangyang Zhou,Bowen Qi,Tao Gong,Xun Sun,Yao Fu,Zhirong Zhang
Parkinson’s disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
研究领域:
神经科学
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药理学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Si Huang,Yong-Jiang Li,Jun-Yong Wu,Xin-Yan Hao,Wen-Jie Xu,Yu-Chen Tang,Min Zhou,Jichun Zhang,Shilin Luo,Da-Xiong Xiang
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG 2000 -levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. Statement of Significance The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA , but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG 2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy.
研究领域:
神经科学
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药学
·
分子生物学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2019
·
IF 2.931
Jianmin Chen,Qinglian Li,Yaling Ye,Ziyao Huang,Zhipeng Ruan,Nan Jin
Tyrosinase is the rate-limiting enzyme for controlling the production of melanin in the human body, and overproduction of melanin can lead to a variety of skin disorders. In this paper, the inhibitory kinetics of phloretin on tyrosinase and their binding mechanism were determined using spectroscopy, molecular docking, antioxidant assays and chromatography. The spectroscopic results indicate that phloretin reversibly inhibits tyrosinase in a mix-type manner through a multiphase kinetic process with the IC 50 of 169.36 μmol/L. It is shown that phloretin has a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting that a stable phloretin-tyrosinase complex is generated. Molecular docking results suggest that the dominant conformation of phloretin binds to the gate of the active site of tyrosinase. Moreover, the antioxidant assays demonstrate that phloretin has powerful antioxidant capacity and has the ability to reduce o -dopaquinone to l -dopa just like ascorbic acid . Interestingly, the results of spectroscopy and chromatography indicate that phloretin is a substrate of tyrosinase but also an inhibitor. The possible inhibitory mechanism is proposed, which will be helpful to design and search for tyrosinase inhibitors.
研究领域:
生物化学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Jiayi Mao,Zhengwei Cai,Zhimo Liu,Shutong Qian,Binfan Zhao,Yuyu Zhang,Yaping Zhuang,Liucheng Zhang,Xiyuan Mao,Yuguang Zhang,Wenguo Cui,Xiaoming Sun
Collecting and utilizing various cytokines released by trauma and implantable materials for stimulating the body in producing a robust immune-inflammatory response would be a promising method. Therefore, an injectable “cytokine reservoir” hydrogel for cytokine management during tissue repair was developed by combining a dual network hydrogel of oxidized glucomannan aldehyde (KGM-CHO) and levodopa-grafted ε-polylysine (EPL-DOPA). The “cytokine reservoir” hydrogel actively recruited macrophages through electrostatic forces and regulated macrophages by mimicking “receptor-ligand” interactions to alter cytokine production patterns. Meanwhile, the dual network hydrogels recruited and stored cytokines by “charge” force then released them according to the degradation of hydrogels, leading to the change of cytokine release pattern. In conclusion, this study provided a unique insight in designing the cytokine management-based tissue engineering strategies for tissue repair.
研究领域:
生物材料
·
组织工程
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2019
·
IF 3.206
Zhao Wang,Hong Yan Yue,Ze Min Yu,Shuo Huang,Xin Gao,Bao Wang,Shan Shan Song,En Hao Guan,Wan Qiu Wang,Hong Jie Zhang
Spherical nickel nanoparticles were prepared by an N 2 H 4 -based solution reduction route. Then, graphene was deposited on the template of nickel nanoparticles by chemical vapor deposition (CVD) at a high temperature. After etching nickel, small-sized, porous and free-standing 3D graphene foam (3D GF) was obtained. It was transferred on the indium tin oxide (ITO) glass (3D GF/ITO) for electrochemical determination of levodopa in the presence/absence of uric acid . The results show that the pore size of the 3D GF is ~1 μm. The electrode shows a high sensitivity of 0.24 μA·μM −1 for the detection of levodopa. The electrode also shows a low measured limit of detection, superior selectivity, reproducibility and stability. Meanwhile, it shows a great potential in the clinical application.
研究领域:
材料科学
·
电化学
·
纳米技术
·
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 21
·5160
·
IF 4.2
Danni Hu,Guanglei Qing,Xuecheng Liu,Jianming Cheng,Kewei Zhang,Lingyun He
Levodopa (LD) is the first discovered and the most promising and effective medication for Parkinson’s disease (PD). As the first identified natural source of LD,Vicia fabaL. (broad beans), especially its sprouts, has been confirmed to contain many other potential bioactive compounds that could also be therapeutic for PD. In this study, the bioactive components obtained from broad bean sprout extraction (BSE) that could be beneficial for PD treatment were screened, and the related mechanisms were explored. Solvent extraction combined with column chromatography was used to isolate bioactive fractions and monomer compounds, while UPLC-ESI-MS/MS, HRESI-MS and (1H,13C) NMR were employed for compound identification. Network pharmacology techniques were applied to screen for potential mechanisms. A total of 52 compounds were identified in a 50% MeOH extract of broad bean sprouts. Moreover, twelve compounds were isolated and identified from ethyl acetate andn-butanol portions, including caffeic acid (1),trans-3-indoleacrylic acid (2),p-coumaric acid (3), protocatechualdehyde (4), isovitexin (5), isoquercetin (6), grosvenorine (7), kaempferol-3-O-rutinoside (8), isoschaftoside (9), narcissin (10), kaempferitrin (11) and trigonelline HCl (12). Compounds2,4,7,8and12were isolated fromVicia fabaL. for the first time. The potential mechanisms were determined by analyzing 557 drug targets, 2334 disease targets and 199 intersections between them using a protein–protein interaction (PPI) network, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment. Further in vitro experiments confirmed that caffeic acid (compound1) andp-coumaric acid (compound3) have neuroprotective effects in 6-hydroxydopamine-treated SH-SY5Y cells and lipopolysaccharide-treated PC-12 cells through anti-inflammatory and antioxidant mechanisms. In conclusion, this study explored effective components in broad bean sprouts and performedin vitroevaluations.
研究领域:
药理学
·
神经科学
·
植物科学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zeyu Qin,Wangyang Fang,Qinbo Jiang,Jiawen Li,Hui Zhang
Inspired by the natural antimicrobial effect of the topographical features of insect wings, this study prepared urchin-like gold nanoparticles (UGNPs) and deposited them on poly(ε-caprolactone) (PCL)/chitosan (P/C) electrospun nanofiber film to strengthen antibacterial activities of this active packaging. Results showed that L-Dopa was a suitable reducing agent to prepare UGNPs, and the spine length of UGNPs increased from 21.23 to 35.83 nm as the molar ratio of L-Dopa:HAuCl 4 increased from 1 to 3. As the nanofiber film was immersed in the nanoparticle solution for a longer time, the UGNP content in P/C nanofibers increased. As the spine length of UGNPs and depositing UGNP content increased, the inhibition rate against S. aureus and E. coli . of P/C nanofiber film increased. In addition, P/C nanofiber film deposited with UGNPs also exhibited good thermal stability , hydrophilicity, mechanical strength , and water vapor permeability, exhibiting its potential as an antibacterial active packaging.
研究领域:
材料科学
·
纳米技术
·
包装工程
·
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）