INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 19
·11572
·
IF 6.208
Chengzhao Li,Jun Dang,Yue Lv,Yan Fang,Chengjun Ma,Qilan Wang,Gang Li
Dracocephalum heterophyllum(D. heterophyllum) is a traditional Chinese Tibetan medicine that has been used for the treatment of lymphitis, hepatitis, and bronchitis. However, only a few selected chemical components are currently obtained fromD. heterophyllum, which limits its further pharmacological applications. In this study, we have obtained samwinol fromD. heterophyllumby medium- and high-pressure liquid chromatography separation for the first time. Thereafter, we investigated the protective actions of samwinol against amyloid beta protein fragment 25–35 (Aβ25–35) induced neurotoxicity in cultured rat pheochromocytoma PC-12 cells and explored its underlying mechanisms of action. The results indicated that samwinol could increase cell viability and inhibit the production of reactive oxygen species (ROS) and mitochondria-derived ROS, as assessed by MTT assay, Giemsa staining, and flow cytometry assay. Through Western blot analysis, it was found that samwinol substantially inhibited the phosphorylation of ERK(1/2) and promoted the expression of HO-1 and Nrf2. The data obtained from molecular docking were also consistent with the above conclusions. All of these results showed that samwinol fromD. heterophyllumcan display significant anti-neuroinflammatory and antioxidant activities in vitro, which are associated with the suppression of ERK/AKT phosphorylation and the activation of the Nrf2/HO-1 signaling pathway. In the future, additional in-depth mechanism studies will be carried out to provide more evidence for the potential of samwinol in the treatment of Alzheimer’s disease.Keywords:D. heterophyllum;PC-12 Cells;Aβ25–35;neuroinflammatory;oxidative stress
研究领域:
药理学
·
神经科学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2016
·
IF 2.653
Chuan-Chuan Zeng,Cheng Zhang,Jun-Hua Yao,Shang-Hai Lai,Bing-Jie Han,Wei Li,Bing Tang,Dan Wan,Yun-Jun Liu
In this article, the in vitro cytotoxicity of platycodin D was evaluated in human PC-12, SGC-7901, BEL-7402, HeLa and A549 cancer cell lines. PC-12 cells were sensitive to platycodin D treatment, with an IC 50 value of 13.5 ± 1.2 μM. Morphological and comet assays showed that platycodin D effectively induced apoptosis in PC-12 cells. Platycodin D increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Platycodin D induced cell cycle arrest at the G0/G1 phase in the PC-12 cell line. Platycodin D can induce autophagy. In addition, platycodin D can down-regulate the expression of Bcl-2 and Bcl-x, and up-regulate the levels of Bid protein in the PC-12 cells. The results demonstrated that platycodin D induced PC-12 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway.
研究领域:
药理学
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细胞生物学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Lu Li,Yuanyuan Fan,Qingling Li,Renjie Sheng,Haibin Si,Juan Fang,Lili Tong,Bo Tang
Various intracellular metal ions have closely related functional roles in the nervous system. An excess or deficiency of essential metal ions can contribute to neurodegenerative diseases. Thus, the detection of various metal ions in neurons is important for diagnosing and monitoring these diseases. In particular, single-cell analysis of multiple metal ions allows us to not only understand the cellular heterogeneity and differentiation but also determine the actual relationships among multiple metal ions in each individual cell. Aiming at the low efficient single-cell manipulation and interference of complex biological matrices within cells in the existing method for single-cell metal ion detection, in this manuscript, we present a convenient, sensitive, and reliable method to simultaneously identify and quantify multiple metal ions at the single-cell level using a microfluidic system. Using the combination of on-chip electrophoresis separation and multicolor fluorescence detection, we achieved the simultaneous analysis of Na+, K+, Ca2+, and Mg2+ in single PC-12 cells and studied changes in these four metal ions in Aβ25–35-treated PC-12 cells, which is a model of Alzheimer’s disease (AD). The data showed that metal ions imbalances in neuron-like cells may be associated with AD induced by Aβ25–35. This method paves the way for multiple metal ion detection in single neuron-like cells, and the results provide insights regarding synergistic function of multiple metal ions in regulation of neurological diseases at the single-cell level.
研究领域:
生物化学
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神经科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 22
·7804
·
IF 4.927
Danyang Zhang,Xia Li,Xiaoshi He,Yan Xing,Bo Jiang,Zhilong Xiu,Yongming Bao,Yuesheng Dong
Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure–activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate group at the 3 position, the pyrogallol group at the B-ring, and theRconfiguration of the 3 position enhanced the protection of flavan-3-ols, and a hydroxyl substitution at the 4′ and meta-positions were important for the protection of flavonol. These SARs were further confirmed by molecular docking using the active site of the Keap1–Nrf2 complex as the receptor. The mechanistic study demonstrated that EGCG with the lowest EC50protected the PC-12 cells from methylglyoxal-induced damage by reducing oxidative stress via the Nrf2/Keap1/HO-1 and Bcl-2/Bax signaling pathways. These results suggested that flavan-3-ols might be a potential dietary supplement for protection against diabetic encephalopathy.Keywords:flavonoids;methylglyoxal;PC-12 cells;structure–activity relationship;oxidative stress;molecular docking
研究领域:
药理学
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神经科学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Linjing Xu,Huan Liu,Yifeng Rang,Lizi Zhou,Xukai wang,Yinhuan Li,Chunhong Liu
Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.
研究领域:
毒理学
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神经科学
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药理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Rongtao Liu,Zebiao Xu,Chen Zhao,Shiyang Zhang,Hongyu Zhou,Li Zhou,Yidong Liu,Yonggang Min
Although electrical stimulation (ES) has been proved to be an effective strategy in promoting the regeneration and repair of injured peripheral nerve tissue, it is still a big challenge to encounter the risk of inflammation and infection when the conductive biological platform directly contacted with the damaged tissue. Therefore, it is a very promising solution to develop non-invasive flexible electrodes’ bio-scaffolds for clinical treatment of nerve tissue regeneration combined with ES. With such purpose, the flexible composite electrodes by depositing polypyrrole on laser-induced graphene (LIG) have been developed. The proliferation and differentiation of PC-12 cells incubated on the prepared composite electrodes combined with an ES of 400 mV/cm at different times have also been investigated. The results showed that the fabricated composite electrodes exhibited excellent conductivity and wettability. Moreover, the essence of ES was to induce a field effect, namely, the cell proliferation was independent of the conductivity of the composite electrodes. In addition, we observed that ES could significantly enhance proliferation and differentiation of PC-12 cells. With the prolongation of ES time, the increasing trend finally stabilized. Importantly, the cell growth through MTT value was 1.37 when ES time was 4 h, and the increment was the largest, reaching 0.3, compared with that of 2 h. Furthermore, the cell differentiation showed that the neurite outgrowth length at 8 h of ES was the broadest distribution (the half-width ca 33.83 μm). And the average neurite length reached 68.39 μm after 8 h of ES, which increased by 16.26 μm compared with that of 4 h. This work inspires the design and construction of a practical conductive platform, and provided a new theoretical basis and data support for clinical therapy in nerve tissue engineering combined with ES.
研究领域:
生物医学工程
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神经科学
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组织工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2021
·
IF 3.512
Junhong Xu,Chunyan Wang,Qiujuan Ma,Hongtao Zhang,Meiju Tian,Jingguo Sun,Baiyan Wang,Yacong Chen
As a key reactive oxygen species (ROS), hypochlorous acid (HClO) plays an important role in many physiological and pathological processes. The mitochondria-targeting probes for the highly sensitive detection of HClO are desirable. In present work, we designed and synthesized an original mitochondria-localizing and turn-on fluorescent probe for detecting HClO. 4-Aminonaphthalimide was employed as the fluorescent section, the (2-aminoethyl)-thiourea unit was utilized as a typical sensing unit, and the quaternized pyridinium moiety was used as a mitochondria-targeted localization group. When HClO was absent, the probe showed weak fluorescence. In the existence of HClO, the probe revealed a blue fluorescence. Moreover, the turn-on fluorescent probe was able to function in a broad pH scope. There was an excellent linearity between the fluorescence emission intensity at 488 nm and the concentrations of HClO in the range of 5.0 × 10–7 to 2.5 × 10–6 mol·L–1. Additionally, the probe had almost no cell toxicity and possessed an excellent mitochondria-localizing capability. Furthermore, the probe was able to image HClO in mitochondria of living PC-12 cells. The above remarkable properties illustrated that the probe was able to determine HClO in mitochondria of living cells.
研究领域:
分析化学
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生物化学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2021
·
IF 6.707
Rongtao Liu,Xingwen Huang,Xiu Wang,Xiaokang Peng,Shiyang Zhang,Yidong Liu,Dong Yang,Yonggang Min
The synergistic effect of endogenous electric field and electrical stimulation (ES) has promising application in the repair and regeneration of injured peripheral nerve. Conducting polymers-based (especially polypyrrole (PPy)) nanofibers have received more attention due to the promotive effects on cell behaviors under ES. However, the conductivity of PPy is unstable and the inferior hydrophilicity hinders its broad applications. Herein, the stable conductive polylactic acid/reduced graphene oxide/polypyrrole (PLA/rGO/PPy) composite nanofibers were prepared by incorporating rGO into PLA, by the following in-situ PPy polymerized on the surface of the PLA/rGO nanofibers. The results show that PPy on the surface of composite nanofibers are dense and continuous, the wettability is significantly improved. With the presence of PPy and rGO, the conductivity and stability of PLA/rGO/PPy composite nanofibers increase, and the conductivity of PLA/rGO 3.5/PPy composite nanofibers was the highest conductivity (1.46 × 10 −1 S/cm). The proliferation and differentiation of PC-12 cells seeded on the surface of PLA/rGO3.5/PPy composite nanofibers reach the highest level under 400 mV/cm. These results are beneficial for improving biomaterial properties and provide guidance to ES application in peripheral nerve repair.
研究领域:
生物医学工程
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神经科学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 67
·42159-42167
·
IF 3.108
Xuewei Zhao,Junli Zhang,Lihong Shi,Ming Xian,Chuan Dong,Shaomin Shuang
Implementing visual detection of cancer cells has the potential to contribute greatly to basic biological research; early diagnosis of cancer is still a challenging issue. In this work, we designed and fabricated folic acid-conjugated fluorescent carbon dots (FA-CDs) for targeted imaging of cancer cells. The green fluorescent CDs were prepared by a facile hydrothermal treatment of dandelion as the carbon source and ethanediamine (EDA). The surfaces of the CDs possessed active amino groups for further covalent conjugation with FA. The uptake of FA-CDs into HepG-2 cells occurs via receptor-mediated endocytosis; this was confirmed by a comparative experiment using FR-negative (FR−) PC-12 cells as revealed by confocal laser scanning microscopy. Intracellular experiments demonstrated that the FA-CDs could accurately recognize positive FR (FR++/FR+) cancer cells in different cell mixtures of MCF-7/HepG-2 cells and HepG-2/PC-12 cells and could distinctly indicate the expression level of FR on the membranes of the cancer cells. The FA-CDs show excellent biocompatibility and low toxicity and may have great potential as an effective tool for accurately differentiating cancer cells from normal cells, in addition to cancer detection, prognosis, and individualized treatment.
研究领域:
生物医学工程
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癌症生物学
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材料科学
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细胞生物学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
eNeuro
·
2024
·
IF 2.7
Yonghong Tan,Qiong Wang,Yubing Guo,Na Zhang,Yingyi Xu,Xue Bai,Jianhua Liu,Xiaobao Bi
Pyroptosis, an inflammatory Programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of proptosis related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced the decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β in lidocaine-induced PC-12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.Significance statement Pyroptosis has been reported to be involved in SCI. Higher levels of CLEC5A, TREM1, and NLRC4 associated with neuronal pyroptosis. However, the role and regulatory mechanism of CLEC5A, TREM1, and NLRC4 in SCI were not clear. Here, high expression of CLEC5A, TREM1, and NLRC4 was observed in lidocaine-induced SCI rat models. CLEC5A could interact with TREM1 to enhance the expression of NLRC4, thus accelerating neuronal pyroptosis in rat SCI models. These findings identify CLEC5A, TREM1, and NLRC4 as potential therapeutic targets for SCI.
研究领域:
神经科学
·
细胞生物学
·
炎症
·
脊髓损伤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 6
·2694-2701
·
IF 3.069
Yuan Zhang,Yang Xing,Ming Xian,Shaomin Shuang,Chuan Dong
Herein, distinctive nanomaterial-based mesoporous silica nanoparticles (MSNs) successively coupled with bovine serum albumin (BSA) and folic acid (FA) were engineered for targeting the release of epirubicin (EPI). The BSA molecule as a “gatekeeper” prevents untimely drug leakage until the BSA coating layer is biodegraded in response to GSH. FA promotes the specific intracellular delivery of the drug to high folate receptor (FR)-expressing cancer cells to improve the efficacy of chemotherapy. In vitro drug release profiles show that this drug carrier can avoid premature release of the drug under physiological conditions, and redox-responsive EPI release from EPI/MSN-FA with easy biodegradability is significantly accelerated in the presence of GSH due to the cleavage of the intramolecular disulfide bond; thus, a “redox-triggered release” of the drug in the simulated targeted tissue microenvironment is achieved. The folate-mediated cellular uptake measured by confocal laser scanning microscopy (CLSM) shows that the hybrid nanoparticles more likely enter the FR-positive (FR+) HepG2 cells than the FR-negative (FR−) PC-12 cells. Toxicity experiment also demonstrates the negligible toxicity of MSN-FA and an increase in the antitumor suppression of EPI/MSN-FA with an increase in the dosage. The results show that the strategy of combining mesoporous silica with protein molecules having stimuli-responsive biodegradability will offer new potential directions towards the “on-demand” drug release for pinpoint chemotherapy in cancer treatment.
研究领域:
纳米技术
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药学
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癌症研究
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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