INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2017
·Vol. 41
·期 2
·1138-1146
·
IF 2.341
Xiu‑Yin Shen,Tao Luo,Sheng Li,Ou‑Yang Ting,Feng He,Jie Xu,Hua‑Qiao Wang
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by aberrant tau protein hyperphosphorylation, which eventually leads to the formation of neurofibrillary tangles. Hyperphosphorylated tau protein is considered as a vital factor in the development of AD and is highly associated with cognitive impairment. Therefore, it is recognized to be a potential therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound. In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced tau protein hyperphosphorylation in HT22 cells was explored. Western blotting results indicated that QUE significantly attenuated OA‑induced tau protein hyperphosphorylation at the Ser396, Ser199, Thr231 and Thr205 sites. Further experiments demonstrated that QUE inhibited the activity of cyclin‑dependent kinase 5 (CDK5), a key enzyme in the regulation of tau protein, and blocked the Ca2+‑calpain‑p25‑CDK5 signaling pathway. These observations indicate the ability of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the associated neuropathology. In conclusion, these results support the potential of QUE as a therapeutic agent for AD and other neurodegenerative tauopathies.
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高影响因子
MARINE ENVIRONMENTAL RESEARCH
·
2025
·
IF 3.2
Jiangbing Qiu,Chao Yin,Aifeng Li,Yongmeng Yang,Guixiang Wang,Dongyue Li
Diarrhetic shellfish toxins (DSTs) are widespread in marine environments, posing potential threats to marine ecosystems, shellfish aquaculture, and human health. Despite their prevalence, knowledge of the stability of dissolved DSTs in seawater is still limited. This study aimed to investigate the effects of bacteria, temperature, and irradiation on the stability of dissolved okadaic acid (OA) and dinophysistoxin-1 (DTX1) in seawater. Results indicated that bacteria did not contribute to the biodegradation of OA and DTX1, while their growth was inhibited by the toxins over the 7-day experiment. During a 28-day period without irradiation at 4°C, 20°C, and 37°C, no degradation of OA was observed, whereas significant degradation of DTX1 occurred, with concentrations dropping to 58% ∼ 78% of the initial concentration at the end of the experiment. Under xenon lamp irradiation at 1000 W, the concentrations of DTX1 decreased by 15% to 19% in seawater after 160 min, while the concentrations of OA showed minimal change. Conversely, both OA and DTX1 underwent significant degradation under mercury lamp irradiation with an irradiation intensity-dependent pattern. Additionally, the degradation rates of OA and DTX1 increased with higher concentrations of dissolved organic matter in the range of 1.2 to 15 mg C L⁻ 1 . This study enhances the understanding of DST stability in seawater under varying temperature and light conditions, highlighting the complexities involved in their degradation processes. The results of this study found that ultraviolet is an important driving environmental factor for OA and DTX1 degradation in the natural marine environment. In case of harmful algal blooms with associated phycotoxins, ultraviolet irradiation can be used as a removal method for OA and DTX1.
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JOURNAL OF CHROMATOGRAPHY A
·
2023
·
IF 4.1
Guomin Qi
A novel three-dimensional covalent organic framework (3D-COF) with content-tunable and active hydroxyl groups (OH) on the pore walls was developed and adopted for the high-performance capture of okadaic acid (OA) marine toxins. Using pore-surface engineering, the integration of linear building blocks (4,4′-diamino-3,3′-biphenyldiol, BD(OH) 2 and benzidine, BD) with the 3D structural building block backbone (4,4′,4′',4′''-methane-tetrayltetrabenzaldehyde, TFPM) was achieved. By adjusting the ratio of BD(OH) 2 , functional multicomponent-COFs [OH] x -BD-TFPM COFs ( X = 25%) were synthesized, which offered ideal access to convert a conventional COF into a functional platform with multiple-mode interactions of hydrophobic and hydrophilic groups for OA capture. [OH] x -BD-TFPM was characterized using SEM, XRD, FT-IR, and BET. The adsorption features and analytical performance of OA were screened and evaluated. Optimization of dispersive solid-phase extraction using [OH] 25 -BD-TFPM was accomplished, and the method was verified for sensitive quantitative detection of OA in clam and mussel samples. Coupled with LC-MS/MS, the resultant [OH] 25 -BD-TFPM COF demonstrated the ability to analyze OA, and the limit of detection for OA in shellfish was determined to be 0.005 μg/kg. A significant improvement in trace OA detection was observed compared to previously reported SPE materials without adjustable hydrophilic interactions. The recoveries of OA in the fortified clam and mussel samples were in the ranges of 93.9‒105.1% and 96.7‒110.2%, respectively. This study highlights that OH-group surface engineering in channel walls is a facile and powerful strategy for developing functional 3D-COFs with multiple interactions for high-performance target capture.
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JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Hui Chen,Chuanhui Huang,Wenming Zhang,Qingqing Ding,Jia Gao,Lan Zhang
An easy-prepared adsorbent with high stable and good dispersibility is especially valuable for the development of magnetic solid-phase extraction (MSPE) techniques. In this study, magnetic nitrogen-doped carbon nanotube cages (N-CNTCs) were synthesized via direct carbonization of cobalt (II)-containing metal-organic frameworks. During carbonization, cobalt ions inside the MOFs were converted into magnetic functional nanoparticles of N-CNTCs. Simultaneously, large amounts of nitrogen, originating from the organic ligands, were doped into the carbon framework. This unique structure gave the N-CNTCs excellent chemical stability, high affinity, and good dispersibility. The synthesized magnetic N-CNTCs were then used for MSPE of okadaic acid (OA) from aquatic samples. A simple, efficient, and sensitive method for detecting and quantitating OA was developed by combining the above sample pretreatment technique with high-performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS). The resulting method boasts a linear dynamic range of 3.0–1000.0 pg mL −1 with good linearity (R 2 ≥ 0.9994). The limit of detection (LOD) and limit of quantification (LOQ) were 1.3 pg mL −1 and 3.0 pg mL −1 , respectively. Several shellfish and seafood samples were analyzed using the developed method, showing satisfactory recoveries (82.0–107.0%) and relative standard deviations (<4.5%). The developed method was also used to investigate the OA distribution in crab tissues. Our results demonstrate that magnetic N-CNTCs are promising adsorbents for providing reliable support for the early warning and tracing to the source of algae toxins.
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PLoS One
·
2016
·Vol. 11
·期 4
·e0152371
·
IF 3.057
Wei Jiang,Tao Luo,Sheng Li,Yue Zhou,Xiu-Yin Shen,Feng He,Jie Xu,Hua-Qiao Wang
Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2018
·Vol. 41
·期 6
·885-890
·
IF 1.694
Zhen-zhen Yuan,You-rui Suo,Xue-yan Hao,Shu-lin Wang,Gang Li,Hong-lun Wang
Six triterpenic acids were separated and purified from the ethyl acetate extractive fraction of ethanol extracts of Potentilla parvifolia FISCH. using a variety of chromatographic methods. The neuroprotective effects of these triterpenoids were investigated in the present study, in which the okadaic acid induced neurotoxicity in human neuroblastoma SH-SY5Y cells were used as an Alzheimer’s disease cell model in vitro. The cell model was established with all trans-retinoic acid (5 µmol/L, 4 d) and okadaic acid (40 nmol/L, 6 h) treatments to induce tau phosphorylation and synaptic atrophy. Subsequently, the neuroprotective effects of these triterpenic acids were evaluated in vitro by this cell model. Results from the Western blot and morphology analysis suggested that compounds 3–6 had the better neuroprotective effects. Furthermore, we tested the level of mitochondrial reactive oxygen species and mitochondrial membrane potential of these compounds in SH-SY5Y cells by flow cytometry technology to investigate the potential neuroprotective mechanism of these compounds. All of the results indicated that maybe the mechanism of compounds 5 and 6 is to protect the cell from mitochondrial oxidative stress injuries.
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CNS & Neurological Disorders-Drug Targets
·
2015
·Vol. 14
·期 10
·1334-1342
·
IF 2.628
Wei Jiang,Wen-Biao Duan,Sheng Li,Xiu-Yin Shen,Yue Zhou,Tao Luo,Feng He,Jie Xu,Hua-Qiao Wang
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by deposit of amyloid plaques and neurofibrillary tangles and oxidative stress plays an essential role in the pathogenesis of AD. Jatrorrhizine (JAT), a Coptidis Rhizome, has multiple biological functions such as anti-oxidation and anti-inflammation. Herein, we investigated the neuroprotective effects of JAT on okadaic acid (OA)- induced cytotoxicity and apoptosis in HT22 cells. Following the exposure to 80nmol/L OA for 12h, the reduction in cell survival, activities of superoxide dismutase, glutathione peroxidase and mitochondria membrane potential has been shown in HT22 cells. In contrast, OA increased levels of lactate dehydrogenase, malondialdehyde production and intracellular reactive oxygen species. OA also enhanced the expression of Bax but decreased the levels of Bcl-2, OA also upregulated the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinases 1/2, phosphorylated c-Jun Nterminal kinases, phosphorylated p38 and NF-kappa B p65 subunit in HT22 cells and this up-regulation was attenuated by JAT which was pre-incubated for 12h in the cells prior to OA exposure. In conclusion, our data present the protective role of JAT in OA induced cytotoxicity, via its antioxidant and anti-apoptotic properties by inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. These results indicate that JAT may be the potential target to treat AD induced by oxidative stress and apoptosis.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2016
·
IF 4.758
Jie Zhou,Xianxin Qiu,Kaiqi Su,Gaixia Xu,Ping Wang
Based on the inhibition of okadaic acid (OA) on protein phosphatase 2A (PP2A), we developed disposable poly- o -aminophenol-carbon nanotubes (PoAP-CNTs) modified screen print electrode (SPE)-based electrochemical enzyme sensor for OA detection. Electropolymerized PoAP-CNTs composite film was coated on electrode for the immobilization of PP2A. Owing to the excellent physicochemical characteristic of PoAP-CNTs film, the performance of enzyme sensor was enhanced. Under the optimal conditions, the biosensor provides a larger linear range, and lower detection limit for the analysis of OA compared with colorimetric PP2A inhibition assay and PP2A/SPE. The spiked OA shellfish samples were applied to verify the efficiency of method for OA detection. The results shows acceptable recovery rate and low RSD, demonstrating the applicability of this method for in suit OA assessment in the quality and toxicity monitoring of seafood.
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JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Hui Chen,Wenmin Zhang,Guancheng Liu,Qingqing Ding,Jinhua Xu,Min Fang,Lan Zhang
Algae toxins pose a severe threat to human health all over the world. In this study, magnetic metal/nitrogen-doped carbon nanotubes (M-NCNTs) were facilely synthesized based on one-step carbonization and applied for magnetic solid-phase extraction of okadaic acid (OA) from seawater followed by high performance liquid chromatographic tandem mass spectrometry (HPLC-MS/MS) analyses. Differences in the physicochemical properties of the three prepared materials (Fe/Co/Ni-NCNTs) were investigated to confirm the best extraction material. Among them, Ni-NCNTs demonstrated a faster extraction rate (10 min) and higher adsorption capacity (223.5 mg g −1 ), mainly due to the higher specific surface area, suitable pore structure and more abundant pyridine nitrogen ring. Under the optimal conditions, the calibration curve was linear over the range (1.0–800.0 pg mL −1 ) with good determination coefficients (R) of 0.9992. The limit of detection (LOD) obtained in multiple replicates was 0.4 pg mL −1 . Three seawater samples were measured by the developed method, 12.3 pg mL −1 of OA was detected with a satisfying recovery (88.6%-106.7%) and acceptable repeatability (RSD ≤ 4.8%, n = 6). The results demonstrate that M-NCNTs materials are a promising candidate for magnetic solid-phase extraction. Benefiting from its high extraction and interference resistance, the established analytical method is expected to be extended to detect other marine environmental pollutions.
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高影响因子
IONICS
·
2021
·Vol. 27
·期 12
·5323-5331
·
IF 2.817
Nai Huimin,Cao Lixin,Sun Shuai,Li Rujin,Liu Haiping,Yan Peisheng
An ultrasensitive label-free electrochemical immunosensor of okadaic acid (OA) was studied based on electrodimerization of p -aminobenzoic acid (p-ABA)-modified gold three-dimensional nanoelectrode ensembles (3DNEEs) which were prepared by electroless gold plating and etching using polycarbonate as template. Staphylococcus protein A (SPA) was introduced to immobilize okadaic acid antibody (anti-OA). The morphology and composition of 3DNEEs were analyzed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDX). The polydimer ( p -aminobenzoic acid) (pPABA) film was measured by Fourier transform infrared spectrometer (FTIR). The concentration of OA was measured by EIS and SWV. The detection limit of EIS is lower than that of SWV (6.47 × 10 −3 ng mL −1 vs. 9.15 × 10 −3 ng mL −1 ), but the linear OA detection range of the latter is wider (0.01–1.0 ng mL −1 vs. 0.01–0.8 ng mL −1 ). The average recovery of OA in oyster samples is 99.81%. The OA recovery test in oyster samples demonstrated potential application value of the electrochemical immunosensor.
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