121 results on '"Cun-Gen Ma"'
Search Results
2. Targeting the differentiation of astrocytes by Bilobalide in the treatment of Parkinson’s disease model
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Li-Juan Song, Ruo-Xuan Sui, Jing Wang, Qiang Miao, Yan He, Jun-Jun Yin, Jun An, Zhi-Bin Ding, Qing-Xian Han, Qing Wang, Jie-Zhong Yu, Bao-Guo Xiao, and Cun-Gen Ma
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General Neuroscience ,General Medicine - Published
- 2022
3. Hydroxysafflor Yellow A exerts neuroprotective effects by inhibiting astrocyte-derived IL-17 after OGD/R
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Lijuan Song, Ke-Xin Liu, Guang-yuan Han, Zhi-bin Ding, Jian-Jun Huang, Bao-Guo Xiao, and Cun-Gen Ma
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Physiology - Abstract
Background: Stroke is the second most common cause of death worldwide, but currently, there exists no effective treatment for stroke. The inflammatory response is a key component of post-stroke and secondary injury. As an inflammatory factor involved in stroke injury, interleukin 17 (IL-17) has become a research hotspot. Hydroxysafflor yellow A (HSYA) has anti-ischemic, anti-oxidation, anti-thrombotic, and anti-inflammatory effects, but whether it has any effect on astrocyte (Ast)-derived IL-17 after cerebral ischemia and hypoxia remains unclear. Its protective effect of neuronal damage caused by IL-17 has not yet been studied. Therefore, in this study, we sought to determine the effect of HSYA on IL-17 and its underlying mechanism, with the aim to provide new ideas for the treatment of ischemic stroke. Methods: The oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary Asts was established, and the effect of HSYA on Ast-derived IL-17 was further verified by experimental methods including Reverse Transcription-Polymerase Chain Reaction(RT-PCR), enzyme-linked immunosorbent assay(ELISA), immunofluorescence and western blot. PC12 cells were cultured with the supernatant of OGD/R astrocytes as conditioned medium for 24h. Lactate dehydrogenase(LDH) and Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) were detected the effect of astrocyte derived IL-17 on PC12 cells. Results: The expression of IL-17 in Asts in the OGD/R group was increased but was decreased after the addition of HSYA. The expression of LCN2 was inhibited, and the inflammatory response and neuronal damage induced by OGD/R were also reduced. PC12 cells were damaged after culturing with Ast-conditioned medium for 24 h; however, the damage was significantly reduced after adding IL-17 neutralizing antibody (ixekizumab antibody) or HSYA. Conclusion: HSYA can inhibit the expression of IL-17 derived from Ast after OGD/R and reduce the binding of IL-17 to IL-17 receptors, thereby protecting neurons. This work was supported by research grants from the National Natural Science Foundation of China (No. 82004028 to L.-J.S., No. 81473577 to C.M.), Innovative Young Talent Team of Shanxi Science and Technology Department (202204051001028 to L.-J.S.), Grant of Zhang Zhongjing Legacy and innovation of State Administration of Traditional Chinese Medicine (GZY-KJS-2022-048-1to L.-J.S.), Young Scientists Cultivation Project of Shanxi University of Chinese Medicine (2021PY-QN-09 to L.S.), Innovation Team of Shanxi University of Chinese Medicine (2022TD2010 to L.S.), Science and Technology Innovation Cultivation Plan of Shanxi University of Chinese Medicine (2022PY-ZBK-006 to L.S.), Leading Team of Medical Science and Technology, Shanxi Province (2020TD05 to C.M.), China Postdoctoral Science Foundation (2020M680912 to L.S.), Cardiovascular special fund project of national regional traditional Chinese medicine medical center of Affifiliated Hospital of Shanxi University of Chinese Medicine in 2021 (XGZX202115 to L.S.), “Basic research project” of the cultivation plan of scientifific and technological innovation ability of Shanxi University of Chinese Medicine (2020PY-JC-02 to L.S.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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- 2023
4. Fasudil alleviates cerebral ischemia‑reperfusion injury by inhibiting inflammation and improving neurotrophic factor expression in rats
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Min‑Fang Guo, Hui‑Yu Zhang, Pei‑Jun Zhang, Yi‑Jin Zhao, Jing‑Wen Yu, Tao Meng, Meng‑Di Li, Na Li, Cun‑Gen Ma, Li‑Juan Song, and Jie‑Zhong Yu
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General Neuroscience ,General Medicine - Abstract
The Rho kinase inhibitor fasudil exerts neuroprotective effects. We previously showed that fasudil can regulate M1/M2 microglia polarization and inhibit neuroinflammation. Here, the therapeutic effect of fasudil on cerebral ischemia‑reperfusion (I/R) injury was investigated using the middle cerebral artery occlusion and reperfusion (MCAO/R) model in Sprague‑Dawley rats. The effect of fasudil on the phenotype of microglia and neurotrophic factors in the I/R brain and its potential molecular mechanism was also explored. It was found that fasudil ameliorated neurological deficits, neuronal apoptosis, and inflammatory response in rats with cerebral I/R injury. Fasudil also promoted the polarization of microglia into the M2 phenotype, in turn promoting the secretion of neurotrophic factors. Furthermore, fasudil significantly inhibited the expression of TLR4 and NF‑κB. These findings suggest that fasudil could inhibit the neuroinflammatory response and reduce brain injury after I/R injury by regulating the shift of microglia from an inflammatory M1 phenotype to an anti‑inflammatory M2 phenotype, which may be related to the regulation of the TLR4/ NF‑κB signal pathway.
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- 2023
5. Wuzi Yanzong pill attenuates MPTP-induced Parkinson’s Disease via PI3K/Akt signaling pathway
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Wei Hang, Hui-jie Fan, Yan-rong Li, Qi Xiao, Lu Jia, Li-juan Song, Yao Gao, Xiao-ming Jin, Bao-guo Xiao, Jie-zhong Yu, Cun-gen Ma, and Zhi Chai
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Cellular and Molecular Neuroscience ,Neurology (clinical) ,Biochemistry - Published
- 2022
6. Corrigendum: Combination therapy with fingolimod and neural stem cells promotes functional myelination in vivo through a non-immunomodulatory mechanism
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Yuan Zhang, Xin-Yu Lu, Ze-Qin Ye, Bogoljub Ciric, Cun-Gen Ma, Abdolmohamad Rostami, Xing Li, and Guang-Xian Zhang
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Cellular and Molecular Neuroscience - Published
- 2022
- Full Text
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7. [Acupuncture ameliorates neurological function by suppressing microglia polarization and inflammatory response after cerebral ischemia in rats]
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Hui-Yu, Zhang, Yi-Jin, Zhao, Pei-Jun, Zhang, Min-Fang, Guo, Jing-Wen, Yu, Zhi, Chai, Cun-Gen, Ma, Li-Juan, Song, and Jie-Zhong, Yu
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Male ,Tumor Necrosis Factor-alpha ,Interleukin-6 ,Brain-Derived Neurotrophic Factor ,NF-kappa B ,Acupuncture Therapy ,Cerebral Infarction ,Rats ,Interleukin-10 ,Rats, Sprague-Dawley ,Toll-Like Receptor 4 ,Reperfusion Injury ,Myeloid Differentiation Factor 88 ,Animals ,Microglia ,Glial Cell Line-Derived Neurotrophic Factor - Abstract
To observe the effect of acupuncture on microglia polarization and inflammatory reaction in rats with cerebral ischemia-reperfusion injury (CIRI), so as to explore its mechanisms underlying improvement of CIRI.Thirty male SD rats were randomly divided into sham operation, model, and acupuncture groups, with 10 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h, followed by reperfusion. After modeling, rats in the acupuncture group received manual acupuncture stimulation of "Dazhui" (GV14), "Baihui"(GV20), "Shuigou" (GV26), bilateral "Zusanli" (ST36) and "Fengchi" (GB20) by twirling the needles rapidly for 10 s/acupoint every 10 min, with the needles retained for 20 min. The treatment was conducted once daily for successive 7 days. The neurological function was evaluated according to Longa's method. The state of CIRI was observed after Nissl staining, and the expression levels of Iba-1, iNOS, Arg1, BDNF, GDNF and NeuN in the ischemic cortex tissue were detected by immunofluorescence staining. The contents of TNF-α, IL-6 and IL-10 in the ischemic tissue were assayed by ELISA. The protein expression levels of BDNF, GDNF, TLR4, MyD88 and NF-κB in the ischemic tissues were detected by Western blot.The neurological deficit score on the 24 h and 7th day was considerably higher in the model group than in the sham operation group (Acupuncture intervention can improve neurological function in CIRI rats, which may be related to its effects in regulating the polarization of microglia, reducing inflammatory reaction and increasing the secretion of neurotrophic factors in the brain, inhibiting TLR4/MyD88/NF-κB signaling pathway.
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- 2022
8. Mdivi-1 Modulates Macrophage/Microglial Polarization in Mice with EAE via the Inhibition of the TLR2/4-GSK3β-NF-κB Inflammatory Signaling Axis
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Xiaojuan Zhang, Yanhua Li, Jie-Zhong Yu, Xiuhua Xue, Xiaojie Niu, Peijun Zhang, Guo-Bin Song, Li-Juan Song, Qing Wang, Xiaoqin Liu, Cun-Gen Ma, and Guoping Xi
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Microglia ,Chemistry ,Experimental autoimmune encephalomyelitis ,Neuroscience (miscellaneous) ,Inflammation ,medicine.disease ,Oligodendrocyte ,Cell biology ,Proinflammatory cytokine ,Cellular and Molecular Neuroscience ,TLR2 ,medicine.anatomical_structure ,Neurology ,medicine ,Macrophage ,Mitochondrial fission ,medicine.symptom - Abstract
Macrophage/microglial modulation plays a critical role in the pathogenesis of multiple sclerosis (MS), which is an inflammatory disorder of the central nervous system. Dynamin-related protein 1 is a cytoplasmic molecule that regulates mitochondrial fission. It has been proven that mitochondrial fission inhibitor 1 (Mdivi-1), a small molecule inhibitor of Drp1, can relieve experimental autoimmune encephalomyelitis (EAE), a preclinical animal model of MS. Whether macrophages/microglia are involved in the pathological process of Mdivi-1-treated EAE remains to be determined. Here, we studied the anti-inflammatory effect of Mdivi-1 on mice with oligodendrocyte glycoprotein peptide35-55 (MOG35-55)-induced EAE. We found that Drp1 phosphorylation at serine 616 in macrophages/microglia was decreased with Mdivi-1 treatment, which was accompanied by decreased antigen presentation capacity of the macrophages/microglia in the EAE mouse spinal cord. The Mdivi-1 treatment caused macrophage/microglia to produce low levels of proinflammatory molecules, such as CD16/32, iNOS, and TNF-α, and high levels of anti-inflammatory molecules, such as CD206, IL-10, and Arginase-1, suggesting that Mdivi-1 promoted the macrophage/microglia shift from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Moreover, Mdivi-1 was able to downregulate the expression of TRL2, TRL4, GSK-3β, and phosphorylated NF-κB-p65 and prevent NF-κB-mediated IL-1β and IL-6 production. In conclusion, these results indicate that Mdivi-1 significantly alleviates inflammation in mice with EAE by promoting M2 polarization by inhibiting TLR2/4- and GSK3β-mediated NF-κB activation.
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- 2021
9. Hyperoside Reduces Rotenone-induced Neuronal Injury by Suppressing Autophagy
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Bo Zhang, Zhi Chai, Wushuai Xiao, Fan Huijie, Li Yanrong, Li-Juan Song, Cun-Gen Ma, Xiaoming Jin, Qing Wang, Jie-Zhong Yu, and Mengying Sun
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Male ,Insecticides ,Cell ,Hyperoside ,Apoptosis ,Caspase 3 ,Pharmacology ,Biochemistry ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,In vivo ,Rotenone ,Autophagy ,medicine ,Animals ,Viability assay ,Membrane Potential, Mitochondrial ,Neurons ,Parkinson Disease ,General Medicine ,Mitochondria ,Rats ,Neuroprotective Agents ,medicine.anatomical_structure ,chemistry ,Quercetin ,Reactive Oxygen Species - Abstract
Hyperoside has a variety of pharmacological activities, including anti-liver injury, anti-depression, anti-inflammatory, and anti-cancer activities. However, the effect of hyperoside on Parkinson's disease (PD) is still unclear. Therefore, we tried to study the therapeutic effect and mechanism of hyperoside on PD in vivo and in vitro models. Rotenone was used to induce PD rat model and SH-SY5Y cell injury model, and hyperoside was used for intervention. Immunohistochemistry, animal behavior assays, TUNEL and Western blot were constructed to observe the protective effect and related mechanisms of hyperoside in vivo. Cell counting kit-8 (CCK-8), flow cytometry, Rh123 staining and Western blot were used for in vitro assays. Rapamycin (RAP) pretreatment was used in rescue experiments to verify the relationship between hyperoside and autophagy in rotenone-induced SH-SY5Y cells. Hyperoside promoted the number of tyrosine hydroxylase (TH)-positive cells, improved the behavioral defects of rats, and inhibited cell apoptosis in vivo. Different concentrations of hyperoside had no significant effect on SH-SY5Y cell viability, but dramatically reversed the rotenone-induced decrease in cell viability, increased apoptosis and loss of cell mitochondrial membrane potential in vitro. Additionally, hyperoside reversed the regulation of rotenone on the Beclin1, LC3II, Bax, cleaved caspase 3, Cyc and Bcl-2 expressions in rat SNpc tissues and SH-SY5Y cells, while promoted the regulation of rotenone on the P62 and α-synuclcin. Furthermore, RAP reversed the effect of hyperoside on rotenone-induced SH-SY5Y cells. Hyperoside may play a neuroprotective effect in rotenone-induced PD rat model and SH-SY5Y cell model by affecting autophagy.
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- 2021
10. Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress
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Yan-rong Li, Hui-jie Fan, Rui-rui Sun, Lu Jia, Li-yang Yang, Hai-fei Zhang, Xiao-ming Jin, Bao-guo Xiao, Cun-gen Ma, and Zhi Chai
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Complementary and alternative medicine ,Pharmacology (medical) ,General Medicine - Abstract
To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice.Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot.Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P0.05). Similarly, WYP increased the total distance and average speed (P0.05 or P0.01), reduced rest time and pole time (P0.05). Moreover, WYP significantly increased TH positive cells (P0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P0.05 or P0.01).WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.
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- 2022
11. Neuroprotective effect of hyperoside in MPP
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Xing-Jie, Xu, Tao, Pan, Hui-Jie, Fan, Xu, Wang, Jie-Zhong, Yu, Hai-Fei, Zhang, Bao-Guo, Xiao, Zhen-Yu, Li, Bo, Zhang, Cun-Gen, Ma, and Zhi, Chai
- Abstract
Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP
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- 2022
12. Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases
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Cun-Gen Ma, Bao-Guo Xiao, Qing Wang, Li-Juan Song, Zhi-Bin Ding, Zhi Chai, and Jie-Zhong Yu
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Developmental Neuroscience - Abstract
Ras homolog (Rho)-associated kinases (ROCKs) belong to the serine-threonine kinase family, which plays a pivotal role in regulating the damage, survival, axon guidance, and regeneration of neurons. ROCKs are also involved in the biological effects of immune cells and glial cells, as well as the development of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation, regulating immune imbalance, repairing the blood-brain barrier, and promoting nerve repair and myelin regeneration. Fasudil, the first ROCKs inhibitor to be used clinically, has a good therapeutic effect on neurodegenerative diseases. Fasudil increases the activity of neural stem cells and mesenchymal stem cells, thus optimizing cell therapy. This review will systematically describe, for the first time, the effects of abnormal activation of ROCKs on T cells, B cells, microglia, astrocytes, oligodendrocytes, and pericytes in neurodegenerative diseases of the central nervous system, summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases, and clarify the possible cellular and molecular mechanisms of ROCKs inhibition. This review also proposes that fasudil is a novel potential treatment, especially in combination with cell-based therapy. Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.
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- 2022
13. Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells
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Qing Wang, Yang-yang Chen, Zhi-chao Yang, Hai-jun Yuan, Yi-wei Dong, Qiang Miao, Yan-qing Li, Jing Wang, Jie-zhong Yu, Bao-guo Xiao, and Cun-gen Ma
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Complementary and alternative medicine ,Pharmacology (medical) ,General Medicine - Abstract
To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P0.05 or P0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P0.05 or P0.01), and inhibited the secretion of inflammatory factors (P0.01 or P0.05). In the central nervous system, GSE inhibited the infiltration of CD45GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
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- 2022
14. Fasudil ameliorates cognitive deficits, oxidative stress and neuronal apoptosis via inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice
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Wen-Yue Wei, Minfang Guo, Qingfang Gu, Jing Zhang, Li-Juan Song, Xiaoqin Liu, Yu-Yin Wang, Zhi Chai, Jie-Zhong Yu, and Cun-Gen Ma
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MAPK/ERK pathway ,Male ,nrf2 ,p38 mitogen-activated protein kinases ,Mice, Transgenic ,Pharmacology ,medicine.disease_cause ,Neuroprotection ,Hippocampus ,Pathology and Forensic Medicine ,Amyloid beta-Protein Precursor ,Mice ,Cognition ,Alzheimer Disease ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,Amyloid precursor protein ,medicine ,Presenilin-1 ,Animals ,oxidative stress ,Protein kinase A ,mapk ,rho-Associated Kinases ,biology ,Chemistry ,Kinase ,Fasudil ,apoptosis ,alzheimer’s disease ,rock ,Mice, Inbred C57BL ,Disease Models, Animal ,NF-E2 Transcription Factor, p45 Subunit ,biology.protein ,Medicine ,Neurology (clinical) ,Oxidative stress ,Signal Transduction - Abstract
Alzheimer's disease (AD) is a severe neurodegenerative disorder of the central nervous system (CNS) characterized by neuron loss and dementia. Previous abundant evidence demonstrates that the first critical step in the course of AD is the state of oxidative stress and the neuronal loss is closely related to the interaction of several signalling pathways. The neuroprotective efficacy of Rho-associated protein kinase (ROCK) inhibitor in the treatment of AD has been reported, but its exact mechanism has not been well elucidated. The purpose of this study is to investigate the therapeutic effects of Fasudil on amyloid precursor protein/presenilin-1 (APP/PS1) mice and to discover the potential underlying mechanism. Sixteen 8-month-old APP/PS1 mice were divided into model and Fasudil treatment groups and 8 wild-type mice were used as a normal control group. After the behavioural test, all mice were sacrificed for immunofluorescence and other biochemical tests. The results showed that the administration of Fasudil improved learning and memory ability, elevated the concentration of antioxidative substances and decreased lipid peroxides, as well as inhibited neuronal apoptosis by increasing the expression of B-cell lymphoma-2 (Bcl-2) (p < 0.05), reducing Bcl-2 Associated X (Bax) (p < 0.05) and cleaved caspase-3 (p < 0.05) of APP/PS1 mice. Moreover, Fasudil treatment also ameliorated the phosphorylation of p38 (p < 0.01), c-Jun N-terminal kinase (JNK) (p < 0.001) and extracellular regulated protein kinases (ERK) (p < 0.001), and accelerated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) (p < 0.01) expression and its antioxidative downstream molecules (p < 0.05, p < 0.05, and p < 0.05, respectively). Data from the present study demonstrate that Fasudil significantly restored cognitive function, restrained oxidative stress and reduced neuronal apoptosis in the hippocampus, probably by inhibiting ROCK/MAPK and activating Nrf2 signalling pathways in APP/PS1 mice.
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- 2021
15. Cloning, Yeast Expression, and Characterization of a β-Amyrin C-28 Oxidase (CYP716A249) Involved in Triterpenoid Biosynthesis in Polygala tenuifolia
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Yu Chen, Cun-Gen Ma, Chenhui Du, Wang Qianyu, Yun-Lan Lian, Tian Hongling, Fu-Sheng Zhang, Xuan Zhang, Min-Sheng Li, Ya-Jie Pu, and Xue-Mei Qin
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0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Amyrin ,Polygala ,Pharmaceutical Science ,Saccharomyces cerevisiae ,Molecular cloning ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cytochrome P-450 Enzyme System ,Biosynthesis ,Triterpene ,Gene Expression Regulation, Plant ,Cloning, Molecular ,Oleanolic Acid ,Oleanolic acid ,Phylogeny ,Pharmacology ,chemistry.chemical_classification ,Oxidase test ,biology ,Arabidopsis Proteins ,General Medicine ,Saponins ,biology.organism_classification ,Triterpenes ,030104 developmental biology ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,Polygala tenuifolia - Abstract
Polygala tenuifolia Willd. is a traditional Chinese herbal medicine that is widely used in treating nervous system disorders. Triterpene saponins in P. tenuifolia (polygala saponins) have excellent biological activity. As a precursor for the synthesis of presenegin, oleanolic acid (OA) plays an important role in the biosynthesis of polygala saponins. However, the mechanism behind the biosynthesis of polygala saponins remains to be elucidated. In this study, we found that CYP716A249 (GenBank: ASB17946) oxidized the C-28 position of β-amyrin to produce OA. Using quantitative real-time PCR, we observed that CYP716A249 had the highest expression in the roots of 2-year-old P. tenuifolia, which provided a basis for the selection of samples for gene cloning. To identify the function of CYP716A249, the strain R-BE-20 was constructed by expressing β-amyrin synthase in yeast. Then, CYP716A249 was co-expressed with β-amyrin synthase to construct the strain R-BPE-20 by using the lithium acetate method. Finally, we detected β-amyrin and OA by ultra-HPLC-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry and GC-MS. The results of this study provide insights into the biosynthesis pathway of polygala saponins.
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- 2020
16. The neuroprotection of hyperoside in MPP+/MPTP -induced Parkinson’s disease model
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Xing-Jie Xu, Tao Pan, Hui-Jie Fan, Xu Wang, Jie-Zhong Yu, Hai-Fei Zhang, Bao-Guo Xiao, Bo Zhang, Cun-Gen Ma, and Zhi Chai
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nervous system - Abstract
BackgroundParkinson's disease (PD) is a neurodegenerative disease featured by the pathological dysfunction of nigrostriatal dopaminergic neurons, which can cause an insufficient release of dopamine (DA), induce motor and nonmotor symptoms. Hyperoside (HYP) belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. This study aimed to investigate the neuroprotective effects of HYP on dopaminergic neurons.Methods and resultsIn this study, MPTP and its active neurotoxic metabolite MPP+ were applied to establish the PD model, respectively, treated with HYP. We found that HYP (100μg/ml) mitigated the cytotoxicity effect of SH-SY5Y cells under the treatment of MPP+ and HYP (25mg/kg/d) alleviated the motor symptoms of PD mice induced by MPTP. HYP treatment reduced the content of NO, H2O2 and malondialdehyde (MDA) as well as mitochondrial damage of DA neurons both in vitro and in vivo. Meanwhile, HYP treatment converted neurotrophic factors' downregulation levels, including GDNF, BDNF and CNDF in vivo but not in nitro. Finally, we found there was an activation of AKT signaling after the administration of HYP in MPP+/MPTP model, and the inhibition of AKT signaling did not block the neuroprotection of HYP on DA neurons. ConclusionsThese results indicate that HYP protected the DA neurons from the MPP+ and MPTP-induced injuries in a way that did not rely on the AKT signal.
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- 2022
17. Drug-induced microglial phagocytosis in multiple sclerosis and experimental autoimmune encephalomyelitis and the underlying mechanisms
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Wen-Yuan Ju, Qing Wang, Li-Juan Song, Zhi-Bin Ding, Xiao-Hui Li, Gajendra Kumar, Yuqing Yan, and Cun-Gen Ma
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Genetics ,General Medicine ,Molecular Biology - Abstract
Microglia are resident macrophages of the central nervous system (CNS). It plays a significant role in immune surveillance under physiological conditions. On stimulation by pathogens, microglia change their phenotypes, phagocytize toxic molecules, secrete pro-inflammatory/anti-inflammatory factors, promotes tissue repair, and maintain the homeostasis in CNS. Accumulation of myelin debris in multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE) inhibits remyelination by decreasing the phagocytosis by microglia and prevent the recovery of MS/EAE. Drug induced microglia phagocytosis could be a novel therapeutic intervention for the treatment of MS/EAE. But the abnormal phagocytosis of neurons and synapses by activated microglia will lead to neuronal damage and degeneration. It indicates that the phagocytosis of microglia has many beneficial and harmful effects in central neurodegenerative diseases. Therefore, simply promoting or inhibiting the phagocytic activity of microglia may not achieve ideal therapeutic results. However, limited reports are available to elucidate the microglia mediated phagocytosis and its underlying molecular mechanisms. On this basis, the present review describes microglia-mediated phagocytosis, drug-induced microglia phagocytosis, molecular mechanism, and novel approach for MS/EAE treatment.
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- 2022
18. The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice
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Si-Si Ren, Qing Wang, Wei Xiao, Liang Cao, Jing Wang, Bao-Guo Xiao, Qing-Xian Han, Jie-Zhong Yu, Cun-Gen Ma, Qiang Miao, Ruo-Xuan Sui, J.Z. Yu, and Xiao-Xue Zhang
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0301 basic medicine ,Encephalomyelitis, Autoimmune, Experimental ,T-Lymphocytes ,T cell ,Central nervous system ,Apoptosis ,Inflammation ,Cyclopentanes ,Biochemistry ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Myelin ,0302 clinical medicine ,medicine ,Animals ,Furans ,Cells, Cultured ,Neuroinflammation ,Microglia ,business.industry ,Macrophages ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,Cell Polarity ,Macrophage Activation ,medicine.disease ,Nerve Regeneration ,Mice, Inbred C57BL ,Oligodendroglia ,Ginkgolides ,030104 developmental biology ,medicine.anatomical_structure ,Remyelination ,Immunology ,Cytokines ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.
- Published
- 2020
19. Anhydrosafflor Yellow B alleviates brain injury of acute permanent cerebral ischemia in rats by anti-inflammatory mechanism
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Ce Zhang, Guang-Yuan Han, Jing Wang, Zhi Chai, Cun-Gen Ma, Jie-Zhong Yu, Li-Juan Song, Jianjun Huang, Bao-Guo Xiao, Qing Wang, Jingping Ma, and Junhong Guo
- Subjects
Ingredient ,Mechanism (biology) ,medicine.drug_class ,Chemistry ,General Neuroscience ,Ischemia ,medicine ,Pharmacology ,General Agricultural and Biological Sciences ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Anti-inflammatory ,Anhydrosafflor yellow B - Abstract
Anhydrosafflor Yellow B (AHSYB), is an effective ingredient with a high content extracted from safflower. The effect of hydroxysafflor yellow A (HSYA), one of the main compounds in safflower, has b...
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- 2020
20. The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer’s disease
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Yi-Ge, Wu, Li-Juan, Song, Li-Jun, Yin, Jun-Jun, Yin, Qing, Wang, Jie-Zhong, Yu, Bao-Guo, Xiao, and Cun-Gen, Ma
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Developmental Neuroscience - Abstract
Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer's disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes; these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer's disease. Our literature search found that phenotypic changes occur continuously in Alzheimer's disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer's disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer's disease.
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- 2023
21. Temporal and Spatial Dynamics of Astroglial Reaction and Immune Response in Cuprizone-Induced Demyelination
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Yan He, Bao-Guo Xiao, Jie-Zhong Yu, Jun An, J.Z. Yu, Jun-Jun Yin, Qing Wang, Qiang Miao, Fu-Dong Shi, Cun-Gen Ma, and Ruo-Xuan Sui
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0301 basic medicine ,Microglia ,biology ,Chemistry ,General Neuroscience ,Ciliary neurotrophic factor ,Toxicology ,Oligodendrocyte ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,nervous system ,medicine ,biology.protein ,Progenitor cell ,Remyelination ,030217 neurology & neurosurgery ,Astrocyte ,Neurotrophin - Abstract
The cuprizone (CPZ)-induced demyelination is a relatively reproducible animal model and has been extremely useful for identifying the specific cellular and molecular signals that regulate oligodendrocyte survival and efficiency of oligodendrogenesis and remyelination. Here, we reported the temporal and spatial dynamics of astroglial reaction and immune response in CPZ-induced demyelinating model. CPZ did not induce significant microglia and astrocyte reaction after 2 weeks of feeding. After 4-6 weeks of CPZ feeding, microglia and astrocytes were markedly migrated and accumulated in myelin sheath. Simultaneously, the expression of tight junction protein ZO-1 was declined and the infiltration of CD4+IFNγ+ and CD4+IL-17+ T cells was increased in the brain, accompanied by increased production of IFN-γ and IL-17 in the extract of brain. However, the levels of IFN-γ and IL-17 were reduced, while IL-6 and TNF-α were elevated in the supernatant of splenocytes. At the 4th and 6th weeks of feeding, CPZ caused astrocyte activation and upregulated the expression of BDNF, CNTF, and IGF-II, providing a neurotrophic microenvironment in the brain. At this stage, NG2+ and PDGF-Rα+ oligodendroglia progenitor cells were enhanced in the corpus callosum, but the myelin sheath is still severely lost. Therefore, targeting microglia to improve the inflammatory microenvironment should contribute to the remyelination.
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- 2019
22. Wuzi Yanzong Pill relieves CPZ-induced demyelination by improving the microenvironment in the brain
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Yan-Rong Li, Meng-Ying Sun, Wei Hang, Qi Xiao, Hui-Jie Fan, Lu Jia, Xiao-Ming Jin, Bo Zhang, Bao-Guo Xiao, Cun-Gen Ma, and Zhi Chai
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Multidisciplinary - Abstract
Wuzi Yanzong Pill (WYP), a well-known prescription for invigorating the kidney and essence, which is widely used to treat infertility such as oligoasthenospermia. Studies have shown that WYP can be used to treat neurological diseases, but its therapeutic effects and mechanisms for multiple sclerosis (MS) remain unclear.Based on the establishment of Cuprizone (CPZ)-induced demyelination model, this study determined the effect of WYP on remyelination by detecting changes in the microenvironment of the central nervous system.C57BL/6 mice were divided into three groups. The CPZ group and CPZ + WYP group were fed with 0.2% CPZ feed, and the control group was fed normal feed, for 6 weeks. At the end of the second week, the CPZ + WYP group was gavaged with WYP solution (16 g/kg/d), and the other two groups were gavaged with normal saline twice a day with an interval of 12 h each time, for 4 weeks. Forced swimming and elevated plus maze were used to detect changes in anxiety and depression before and after treatment. Luxol fast blue staining and the expression of MBP were used to evaluate the demyelination of the brain. Western blot was used to detect the expression of microglia and their subtype markers Iba-1, Arg-1, iNOS, the expression of neurotrophic factors BDNF, GDNF, CNTF, and the expression of oligodendrocyte precursor cells NG2. ELISA detected the content of IL-6, IL-1β, IL-10, TGF-β, BDNF, GDNF, CNTF in the brain. The distribution of Iba-1 in the corpus callosum was observed by immunofluorescence.The results showed that on the basis of improving mood abnormalities and demyelination, WYP reduced the protein content of Iba-1 and iNOS, increased the protein content of Arg-1, and reduce accumulation of microglia in the corpus callosum. In addition, WYP reduced the secretion of IL-6 and IL-1β while promoting the secretion of IL-10 and TGF-β. After WYP intervention treatment, the levels of neurotrophic factors BDNF, GDNF, CNTF increased. Due to the improvement of inflammatory and nutritional environment in the CNS, promoting the proliferation of NG2 oligodendrocyte, increased the expression of MBP, and repairing myelin sheath.Our results indicated that WYP promoted the proliferation and development of oligodendrocytes by improving the CNS microenvironment, effectively alleviating demyelination.
- Published
- 2022
23. Blocking receptor for advanced glycation end-products (RAGE) or toll like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice
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Xiaoming Jin, Cun-Gen Ma, Zhi Chai, Fletcher Fa White, Weiping Wang, and Xingjie Ping
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medicine.medical_specialty ,Glutamate decarboxylase ,Receptor for Advanced Glycation End Products ,Epileptogenesis ,Article ,RAGE (receptor) ,Mice ,Seizures ,Internal medicine ,medicine ,Animals ,Pentylenetetrazol ,Neuroinflammation ,Mice, Knockout ,Epilepsy ,Seizure threshold ,business.industry ,Epilepsy, Post-Traumatic ,Toll-Like Receptor 4 ,Disease Models, Animal ,Endocrinology ,Neurology ,Knockout mouse ,TLR4 ,Pentylenetetrazole ,Neurology (clinical) ,business ,medicine.drug - Abstract
OBJECTIVE Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis. METHODS In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology. RESULTS Undercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p
- Published
- 2021
24. Fasudil-Triggered Phagocytosis of Myelin Debris Promoted Meylin Regeneration via the Activation of TREM2/DAP12 Signaling Pathway in Cuprizone-Induced Mice
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Zhi-Bin Ding, Bao-Guo Xiao, Cun-Gen Ma, Y.H. Li, Jie-Zhong Yu, Guo-Guo Chu, Guang-Yuan Han, Li-Juan Song, Qing-Xian Han, Zhi Chai, and Qing Wang
- Subjects
Myelin ,medicine.anatomical_structure ,TREM2 ,Chemistry ,Phagocytosis ,Regeneration (biology) ,medicine ,Fasudil ,Signal transduction ,Cell biology - Abstract
The inflammation and demyelination of the central nervous system (CNS) are mainly involved in multiple sclerosis (MS), in which the disorder of myelin regeneration leads to continual neurologic impairment. Fasudil, one of the ROCK inhibitors, has been shown protective functions in some models of demyelinating diseases. In this study, Fasudil treatment ameliorated the behavioral performance and myelin loss in CPZ-fed mice. Here, we demonstrated a new role of Fasudil, which triggered microglia to uptake myelin debris in both cell and animal experiments. This increased phagocytosis was associated with the polarization of M2 microglia. Furthermore, we found that Fasudil enhanced the expression of triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12), which regulated microglial phagocytosis and M2 polarization. The silence of TREM2 effectively blocked Fasudil-triggered phagocytic capacity, suggesting that Fasudil-triggered phagocytosis depends on TREM2 signaling pathway. Based on these evidences that TREM2 regulates microglial M2 polarization and phagocytosis, future studies targeted Fasudil as a therapy for demyelinating and neurodegenerative diseases are warranted.
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- 2021
25. Retracted: Effect of Fasudil on remyelination following cuprizone‐induced demyelination
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Bao-Guo Xiao, Li-Juan Song, Jie-Zhong Yu, Jing Wang, Qiang Miao, Yan-Hua Li, Ruo-Xuan Sui, Cun-Gen Ma, and Qing Wang
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0301 basic medicine ,Pharmacology ,biology ,Microglia ,Chemistry ,Fasudil ,Ciliary neurotrophic factor ,Luxol fast blue stain ,Myelin basic protein ,Myelin oligodendrocyte glycoprotein ,03 medical and health sciences ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Physiology (medical) ,biology.protein ,medicine ,Pharmacology (medical) ,Remyelination ,030217 neurology & neurosurgery ,Neuroinflammation - Abstract
Background Multiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)-induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors. Methods Following CPZ exposure, the degree of demyelination in the brain of male C57BL/6 mice was assessed by Luxol fast blue, Black Gold II, myelin basic protein immunofluorescent staining, and Western blot. The effect of Fasudil on behavioral change was determined using elevated plus maze test and pole test. The possible mechanisms of Fasudil action were examined by immunohistochemistry, flow cytometry, ELISA, and dot blot. Results Fasudil improved behavioral abnormalities, inhibited microglia-mediated neuroinflammation, and promoted astrocyte-derived nerve growth factor and ciliary neurotrophic factor, which should contribute to protection and regeneration of oligodendrocytes. In addition, Fasudil inhibited the production of myelin oligodendrocyte glycoprotein antibody and the infiltration of peripheral CD4+ T cells and CD68+ macrophages, which appears to be related to the integrity of the blood-brain barrier. Conclusion These results provide evidence for the therapeutic potential of Fasudil in CPZ-induced demyelination. However, how Fasudil acts on microglia, astrocytes, and immune cells remains to be further explored.
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- 2019
26. The therapeutic potential of ginkgolide K in experimental autoimmune encephalomyelitis via peripheral immunomodulation
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Wen-Bo Yu, Wei Xiao, Liang Cao, Jie Tang, Sheng Chen, Qing Wang, Bao-Guo Xiao, and Cun-Gen Ma
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0301 basic medicine ,Cell type ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Immunology ,Central nervous system ,Anti-Inflammatory Agents ,Pharmacology ,T-Lymphocytes, Regulatory ,Lactones ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Demyelinating disease ,Animals ,Humans ,Immunology and Allergy ,Platelet Activating Factor ,Th1-Th2 Balance ,Cells, Cultured ,Chemistry ,Chemotaxis ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,Cell Differentiation ,Cell migration ,medicine.disease ,Spinal cord ,Mice, Inbred C57BL ,Disease Models, Animal ,Ginkgolides ,030104 developmental biology ,medicine.anatomical_structure ,Cellular Microenvironment ,030220 oncology & carcinogenesis ,TLR4 ,Cytokines ,Th17 Cells ,Female ,Microglia - Abstract
Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.
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- 2019
27. RETRACTED: Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model
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Ruo-Xuan Sui, Jing Wang, Cun-Gen Ma, Qiang Miao, Yan-Hua Li, Li-Juan Song, Bao-Guo Xiao, Qing Wang, and Jie-Zhong Yu
- Subjects
CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Immunology ,Motor Activity ,Myelin oligodendrocyte glycoprotein ,Cuprizone ,Myelin ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,Internal medicine ,medicine ,Demyelinating disease ,Animals ,Immunology and Allergy ,Remyelination ,Neuroinflammation ,Behavior, Animal ,biology ,Microglia ,Chemistry ,Macrophages ,Multiple sclerosis ,Brain ,medicine.disease ,Oligodendrocyte ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,nervous system ,biology.protein ,Cytokines ,Spleen ,Demyelinating Diseases - Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system characterized by oligodendrocyte loss and progressive neurodegeneration. The cuprizone (CPZ)-induced demyelination is widely used to investigate the demyelination/remyelination. Here, we explored the therapeutic effects of Hydroxyfasudil (HF), an active metabolite of Fasudil, in CPZ model. HF improved behavioral abnormality and reduced myelin damage in the corpus callosum. Splenic atrophy and myelin oligodendrocyte glycoprotein (MOG) antibody were observed in CPZ model, which were partially restored and obviously inhibited by HF, therefore reducing pathogenic binding of MOG antibody to oligodendrocytes. HF inhibited the percentages of CD4+IL-17+ T cells from splenocytes and infiltration of CD4+ T cells and CD68+ macrophages in the brain. HF also declined microglia-mediated neuroinflammation, and promoted the production of astrocyte-derived brain derived neurotrophic factor (BDNF) and regeneration of NG2+ oligodendrocyte precursor cells. These results provide potent evidence for the therapeutic effects of HF in CPZ-induced demyelination.
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- 2019
28. Nasal delivery of Fasudil-modified immune cells exhibits therapeutic potential in experimental autoimmune encephalomyelitis
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Qing Wang, Shang-de Guo, Guo-Bin Song, Cun-Gen Ma, Chun-Yun Liu, Yan-Hua Li, Zhi Chai, Ling Feng, J.Z. Yu, Xi-Ting Mi, Peng-Wei Yang, and Bao-Guo Xiao
- Subjects
0301 basic medicine ,Encephalomyelitis, Autoimmune, Experimental ,Cell- and Tissue-Based Therapy ,experimental autoimmune encephalomyelitis ,Pharmacology ,Myelin oligodendrocyte glycoprotein ,Cell therapy ,Fasudil‐modified mononuclear cells ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neurotrophic factors ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,Physiology (medical) ,medicine ,Animals ,Pharmacology (medical) ,Protein Kinase Inhibitors ,Administration, Intranasal ,biology ,business.industry ,nasal delivery ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,Fasudil ,Original Articles ,medicine.disease ,Peptide Fragments ,Mice, Inbred C57BL ,Psychiatry and Mental health ,030104 developmental biology ,Spinal Cord ,Leukocytes, Mononuclear ,biology.protein ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Original Article ,Nasal administration ,cell therapy ,business ,030217 neurology & neurosurgery - Abstract
Aim Multiple sclerosis (MS) is a relapsing-remitting inflammatory demyelinating disease that requires long-term treatment. Although Rho kinase inhibitor Fasudil shows good therapeutic effect in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, certain side effects may limit its clinical use. This study aimed at observing the therapeutic potential of Fasudil-modified encephalitogenic mononuclear cells (MNCs) via nasal delivery in EAE and exploring possible mechanisms of action. Methods Experimental autoimmune encephalomyelitis was induced with myelin oligodendrocyte glycoprotein 35-55 in C57BL/6 mice, and encephalitogenic MNCs were treated with Fasudil in vitro. Mice received 3 × 106 cells/10 μL per nasal cavity on day 3 and 11 postimmunization, respectively. Results Fasudil-modified MNCs reduced clinical severity of EAE, improved demyelination, and decreased inflammatory cells in spinal cords. Immunohistochemical results indicated that CD4+ T cells and CD68+ macrophages were barely detected in Fasudil-MNCs group. Fasudil-modified MNCs decreased CD4+ IFN-γ+ and CD4+ IL-17+ T cells, increased CD4+ IL-10+ T cells, restrained M1 markers CD16/32, CCR7, IL-12, CD8a, enhanced M2 markers CD206, CD200, CD14 in spleen. Fasudil-modified MNCs inhibited the activation of inflammatory signaling p-NF-kB/P38, accompanied by the decrease of COX-2 and the increase of Arg-1 in spinal cord, as well as the reduction of IL-17, TNF-α, IL-6 and the elevation of IL-10 in cultured supernatant of splenocytes. Fasudil-modified MNCs enhanced the levels of neurotrophic factors BDNF and NT-3 in spinal cord. Conclusion Our results indicate that intranasal delivery of Fasudil-modified MNCs have therapeutic potential in EAE, providing a safe and effective cell therapeutic strategy to MS and/or other related disorders.
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- 2019
29. The mechanism of grape seed oligomeric procyanidins in the treatment of experimental autoimmune encephalomyelitis mice
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Y.H. Li, Li-Juan Song, Yingli Wang, Yanhua Li, Liyuan Xue, Zhi-Bin Ding, Jie-Zhong Yu, Qing Wang, Cun-Gen Ma, and Qiang Miao
- Subjects
Chemistry ,Mechanism (biology) ,Experimental autoimmune encephalomyelitis ,medicine ,medicine.disease ,Grape seed ,Cell biology - Abstract
Objective This study aims to investigate the mechanism of grape seed oligomeric procyanidins (GPC) in the treatment of experimental autoimmune encephalomyelitis (EAE) mice, providing pharmacodynamic materials for drug development in the treatment of multiple sclerosis (MS). Methods The constituents which have nerve protective effect in GPC were collected through literature retrieval. We used PharmMapper and STITCH database to predict drug targets, GeneCards and OMIM database to predict MS-related genes. Targets of GPC treating MS were obtained from intersected targets between drug and disease. The GO functional enrichment and KEGG pathway enrichment analysis were performed by DAVID database. EAE mouse model was used to study the therapeutic mechanism of GPC. Results Forty-two targets were discovered to be related to the process of GPC treating MS. KEGG enriched a total of 32 pathways. The pharmacological experiment showed that GPC improved the clinical symptoms of EAE mice, inhibited the expression of indicators of oxidative stress and inflammatory response in CNS, and decreased the expression of P-Akt, P-ERK, and P-JNK. Conclusion The therapeutic effect of GPC in EAE mice is associated with the suppression of MAPK and PI3K-Akt signaling pathways, providing a theoretical basis for the application of GPC inMS.
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- 2021
30. Ethyl Pyruvate–Derived Transdifferentiation of Astrocytes to Oligodendrogenesis in Cuprizone-Induced Demyelinating Model
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Qing-Xian Han, Jun-Jun Yin, Jun An, Bao-Guo Xiao, Ruo-Xuan Sui, Qiang Miao, Jianjun Huang, Zhi-Bin Ding, Yan He, and Cun-Gen Ma
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0301 basic medicine ,Ciliary neurotrophic factor ,Carboxyfluorescein diacetate succinimidyl ester ,03 medical and health sciences ,Myelin ,chemistry.chemical_compound ,Cuprizone ,Mice ,0302 clinical medicine ,Phagocytosis ,medicine ,Animals ,Pharmacology (medical) ,Translation factor ,Pyruvates ,Pharmacology ,Membrane Glycoproteins ,biology ,Chemistry ,Transdifferentiation ,Receptors, Interleukin-1 ,Nestin ,Cell biology ,Transplantation ,Mice, Inbred C57BL ,Disease Models, Animal ,Oligodendroglia ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Astrocytes ,Cell Transdifferentiation ,biology.protein ,Original Article ,Neurology (clinical) ,030217 neurology & neurosurgery ,Astrocyte ,Demyelinating Diseases - Abstract
Astrocytes redifferentiate into oligodendrogenesis, raising the possibility that astrocytes may be a potential target in the treatment of adult demyelinated lesion. Upon the basis of the improvement of behavior abnormality and demyelination by ethyl pyruvate (EP) treatment, we further explored whether EP affects the function of astrocytes, especially the transdifferentiation of astrocytes into oligodendrogenesis. The results showed that EP treatment increased the accumulation of astrocytes in myelin sheath and promoted the phagocytosis of myelin debris by astrocytes in vivo and in vitro. At the same time, EP treatment induced astrocytes to upregulate the expression of CNTF and BDNF in the corpus callosum and striatum as well as cultured astrocytes, accompanied by increased expression of nestin, Sox2, and β-catenin and decreased expression of Notch1 by astrocytes. As a result, EP treatment effectively promoted the generation of NG2+ and PDGF-Ra+ oligodendrocyte precursor cells (OPCs) that, in part, express astrocyte marker GFAP. Further confirmation was performed by intracerebral injection of primary astrocytes labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE). As expected, NG2+ OPCs expressing CFSE and Sox2 were elevated in the corpus callosum of mice treated with EP following transplantation, revealing that EP can convert astrocytes into myelinating cells. Our results indicate the possibility that EP lead to effective myelin repair in patients suffering from myelination deficit.Graphical Abstract The diagram of EP action for promoting myelin regeneration in CPZ model. EP promoted migration and enrichment of astrocytes to demyelinated tissue and induced astrocytes to express neurotrophic CNTF and BDNF as well as translation factor nestin, Sox2, and β-catenin, which should contribute to astrocytes to differentiate of oligodendrogenesis. At the same time, EP promoted astrocytes to phagocytized myelin debris for removing the harmful substances of myelin regeneration.
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- 2020
31. The neuroprotective effects and transdifferentiation of astrocytes into dopaminergic neurons of Ginkgolide K on Parkinson’ disease mice
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Qiang Miao, Zhi Chai, Li-Juan Song, Qing Wang, Guo-Bin Song, Jing Wang, Jie-Zhong Yu, Bao-Guo Xiao, and Cun-Gen Ma
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Male ,Dopaminergic Neurons ,Immunology ,Mice, Inbred C57BL ,Lactones ,Mice ,Ginkgolides ,Neuroprotective Agents ,Parkinsonian Disorders ,Neurology ,Astrocytes ,Cell Transdifferentiation ,Animals ,Immunology and Allergy ,Neurology (clinical) - Abstract
Parkinson's disease (PD) is a chronic and progressive movement disorder caused by the selective loss of midbrain dopaminergic neurons of unknown etiology. Up to now, although there is a great development on treatments of PD, cures with neuroprotective or nerve regenerative effects are underway for PD patients. Here we reported neuroprotective effects of Ginkgolide K (GK) when mice were upon acute MPTP exposure, in which GK ameliorated the gait dysfunction and dopaminergic neuron loss. GK exhibits its ability in immunomodulation, including switching microglia to M2 phenotype and decreasing the microglia-mediated inflammation, inhibiting peripheral CD4
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- 2022
32. Fasudil enhances the phagocytosis of myelin debris and the expression of neurotrophic factors in cuprizone-induced demyelinating mice
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Qing Wang, Zhi-Bin Ding, Minfang Guo, Guo-Guo Chu, Li-Juan Song, Qing-Xian Han, Xin-Yi Li, Cun-Gen Ma, Zhi Chai, Jie-Zhong Yu, and Bao-Guo Xiao
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0301 basic medicine ,Male ,03 medical and health sciences ,Myelin ,Cuprizone ,Mice ,0302 clinical medicine ,Phagocytosis ,Neurotrophic factors ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,Glial cell line-derived neurotrophic factor ,medicine ,Animals ,Humans ,Glial Cell Line-Derived Neurotrophic Factor ,Remyelination ,Neuroinflammation ,Myelin Sheath ,biology ,Microglia ,Chemistry ,General Neuroscience ,Brain-Derived Neurotrophic Factor ,Fasudil ,Cell Differentiation ,Cell biology ,Disease Models, Animal ,Oligodendroglia ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Rho kinase inhibitor ,biology.protein ,030217 neurology & neurosurgery ,Demyelinating Diseases - Abstract
Multiple sclerosis (MS) is mainly associated with the neuroinflammation and demyelination in the central nervous system (CNS), in which the failure of remyelination results in persistent neurological dysfunction. Fasudil, a typical Rho kinase inhibitor, has been exhibited beneficial effects on several models of neurodegenerative disorders. In this study, we showed that Fasudil promoted the uptake of myelin debris by microglia via cell experiments and through a cuprizone (CPZ)-induced demyelinating model. In vitro, microglia with phagocytic debris exhibited enhanced expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), and the conditioned medium promoted the maturation of oligodendrocyte precursor cells (OPCs). Meanwhile, Fasudil upregulated TREM2/DAP12 pathway, which positively regulated the phagocytosis of myelin debris by microglia. Similarly, in vivo, Fasudil intervention enhanced the clearance of myelin debris, upregulated the expression of BDNF and GDNF on microglia, and promoted the formation of Oligo2+/PDGFRα+ OPCs and the maturation of MBP + oligodendrocytes in the brain. Our results showed that Fasudil targeted the phagocytic function of microglia, effectively clearing myelin debris produced during pathological process possibly by upregulating TREM2/DAP12 pathway, accompanied by increased expression of BDNF and GDNF. However, the precise mechanism underlying the effects of Fasudil in promoting phagocytic effects and neurotrophic factors remains to be elucidated.
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- 2020
33. Dynamic Balance of Microglia and Astrocytes Involved in the Remyelinating Effect of Ginkgolide B
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Jun-Jun Yin, Qing Wang, Yan He, Qiang Miao, Ruo-Xuan Sui, Cun-Gen Ma, Bao-Guo Xiao, Jie-Zhong Yu, and Jun An
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0301 basic medicine ,microglia ,Neuroprotection ,lcsh:RC321-571 ,03 medical and health sciences ,Myelin ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Neurotrophic factors ,medicine ,cuprizone-induced demyelination ,Remyelination ,Demyelinating Disorder ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroinflammation ,Original Research ,Microglia ,Chemistry ,Multiple sclerosis ,astrocytes ,medicine.disease ,Ginkgolide B ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,remyelination ,Cellular Neuroscience ,030217 neurology & neurosurgery - Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disorder in the central nervous system (CNS), in which remyelination failure results in persistent neurologic impairment. Ginkgolide B (GB), a major terpene lactone and active component of Ginkgo biloba, has neuroprotective effects in several models of neurological diseases. Here, our results show, by using an in vivo cuprizone (CPZ)-induced demyelinating model, administration of GB improved behavior abnormalities, promoted myelin generation, and significantly regulated the dynamic balance of microglia and astrocytes by inhibiting the expression of TLR4, NF-κB and iNOS as well as IL-1β and TNF-α, and up-regulating the expression of Arg-1 and neurotrophic factors. GB treatment also induced the generation of oligodendrocyte precursor cells (OPCs). In vitro cell experiments yielded the results similar to those of the in vivo model. The dynamic balance by decreasing microglia-mediated neuroinflammation and promoting astrocyte-derived neurotrophic factors should contribute to endogenous remyelination. Despite GB treatment may represent a novel strategy for promoting myelin recovery, the precise mechanism of GB targeting microglia and astrocytes remains to be further explored.
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- 2020
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34. Graphene-Based Nanomaterials: Potential Tools for Neurorepair
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Wei-Jia Jiang, Qing Wang, Jian-Guo Zhao, Yan-Hua Li, Guang-Xian Zhang, Cun-Gen Ma, and Bao-Guo Xiao
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Pharmacology ,Materials science ,Biocompatibility ,Graphene ,Biocompatible Materials ,Cell Differentiation ,030208 emergency & critical care medicine ,Nanotechnology ,Nanostructures ,Nanomaterials ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Neural Stem Cells ,law ,Drug Discovery ,Drug delivery ,Cell Adhesion ,Humans ,Graphite ,Cell Proliferation - Abstract
Graphene, with its outstanding electrical properties, large surface area, and excellent mechanical properties, is found in a wide variety of applications in biomimetic substrates and biomedicine, with the result that there is growing interest in the effect of graphene-based nanomaterials on neural cells. This review sums up current research on the effectiveness of graphene and its derivatives on neural cells. We emphasize the biocompatibility of graphene and its derivatives, and how they affect the behavior of neural cells, including adhesion, proliferation, neurite outgrowth and differentiation. In addition, we discuss at great length the literature on graphenebased nanomaterials for drug delivery applications. While their in vivo effects on the nervous system remain to be explored, encouraging findings indicate that graphene-based nanomaterials have significant potential as novel therapies for neurodegenerative disease.
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- 2018
35. The neuroprotective effects of Ginkgolide K on MPTP mice
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Li-Juan Song, Bao-Guo Xiao, Cun-Gen Ma, Qiang Miao, Qing Wang, Xiao-Hui Li, Jie-Zhong Yu, Tao Meng, Jing Wang, Z. Chai, Y.H. Li, and J.J. Huang
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chemistry.chemical_compound ,Neurology ,Chemistry ,MPTP ,Neurology (clinical) ,Pharmacology ,Ginkgolide K ,Neuroprotection - Published
- 2021
36. The mechanism of Wuzi Yanzong Pill in the prevention and treatment of Parkinson's disease based on PI3K-AKT signaling pathways
- Author
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L.J. Song, Lu Jia, Hui Jie Fan, Cun Gen Ma, Bao Guo Xiao, Yan Rong Li, Z. Chai, Wei Hang, Meng Ying Sun, J.J. Huang, and Jie Zhong Yu
- Subjects
Pi3k akt signaling ,Parkinson's disease ,Neurology ,Mechanism (biology) ,business.industry ,Wuzi yanzong ,Pill ,medicine ,Neurology (clinical) ,Pharmacology ,medicine.disease ,business - Published
- 2021
37. Fasudil protects neurons through inhibiting oxidative stress response and restoring mitochondrial fission-fusion imbalance
- Author
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Yu-Yin Wang, Wen-Yue Wei, Minfang Guo, Li-Juan Song, Z. Chai, J.J. Huang, Dong Ma, Qingfang Gu, Jing Zhang, Jie-Zhong Yu, Cun-Gen Ma, and Su-Yao Li
- Subjects
Neurology ,Chemistry ,Fasudil ,medicine ,Mitochondrial fission ,Neurology (clinical) ,medicine.disease_cause ,Oxidative stress ,Cell biology - Published
- 2021
38. Research on the mechanism of Wuzi Yanzong Pill excluding folic acid interference in the prevention and control of neural tube defects
- Author
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Chan Juan Yang, Wu Shuai Xiao, Jie Zhong Yu, Meng Ying Sun, Hui Jie Fan, Bao Guo Xiao, Xin Liang Wang, Z. Chai, Yi Ru, Cun Gen Ma, J.J. Huang, and Yan Rong Li
- Subjects
medicine.anatomical_structure ,Neurology ,Folic acid ,Chemistry ,Mechanism (biology) ,Wuzi yanzong ,Neural tube ,medicine ,Neurology (clinical) ,Pharmacology ,Interference (genetic) - Published
- 2021
39. Research on the prevention and treatment of experimental autoimmune encephalomyelitis by Wuzi Yanzong pill based on endoplasmic reticulum stress pathway
- Author
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L.J. Song, Wu Shuai Xiao, Hui Jie Fan, Bao Guo Xiao, Cun Gen Ma, Yan Rong Li, Chan Juan Yang, Meng Ying Sun, Jie Zhong Yu, Z. Chai, Lu Jia, and J.J. Huang
- Subjects
Neurology ,business.industry ,Endoplasmic reticulum ,Wuzi yanzong ,Pill ,Experimental autoimmune encephalomyelitis ,Medicine ,Neurology (clinical) ,Pharmacology ,business ,medicine.disease - Published
- 2021
40. Icariin inhibits demyelination by targeting the phagecytic activity of microglia in CPZ-induced demyelinating mice
- Author
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Qing-Xian Han, Cun-Gen Ma, Qing Wang, Z. Chai, Zhi-Bin Ding, Qiang Miao, Bao-Guo Xiao, Li-Juan Song, J.Z. Yu, J.J. Huang, Ru-Heng Wei, and Jie-Zhong Yu
- Subjects
chemistry.chemical_compound ,medicine.anatomical_structure ,Neurology ,Microglia ,Chemistry ,medicine ,Neurology (clinical) ,Pharmacology ,Icariin - Published
- 2021
41. Wuzi Yanzong Pill, A classical herbal formula, exhibits therapeutic potential in treating Parkinson's disease
- Author
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Hui Jie Fan, Yan Rong Li, Cun Gen Ma, J.Z. Yu, Meng Ying Sun, Wu Shuai Xiao, Bao Guo Xiao, Z. Chai, and J.J. Huang
- Subjects
Parkinson's disease ,Neurology ,Traditional medicine ,business.industry ,Pill ,Wuzi yanzong ,Medicine ,Neurology (clinical) ,business ,medicine.disease - Published
- 2021
42. Fasudil promoted remyelination in CPZ-induced mice by regulating the function of astrocytes
- Author
-
J.J. Huang, Zhi-Bin Ding, Qing-Xian Han, Jie-Zhong Yu, Li-Juan Song, Qing Wang, Bao-Guo Xiao, Minfang Guo, Z. Chai, Wen-Yuan Ju, Yang-Yang Chen, and Cun-Gen Ma
- Subjects
medicine.anatomical_structure ,Neurology ,Chemistry ,Fasudil ,medicine ,Neurology (clinical) ,Pharmacology ,Remyelination ,Function (biology) - Published
- 2021
43. Wuzi Yanzong pills relieve CPZ-induced demyelination by improving the microenvironment in the brain
- Author
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Meng Ying Sun, Yan Rong Li, Jie Zhong Yu, Hui Jie Fan, Wu Shuai Xiao, J.J. Huang, Qing Wang, Cun Gen Ma, Z. Chai, Lu Jia, Bao Guo Xiao, and Wei Hang
- Subjects
Neurology ,business.industry ,Wuzi yanzong ,Medicine ,Neurology (clinical) ,Pharmacology ,business - Published
- 2021
44. The regulatory effect of Wuzi Yanzong pill on UPR signaling pathway in Parkinson's disease mice
- Author
-
Bao Guo Xiao, Yan Rong Li, Z. Chai, Jie Zhong Yu, Wu Shuai Xiao, Hui Jie Fan, J.J. Huang, Cun Gen Ma, Wei Hang, and Meng Ying Sun
- Subjects
Parkinson's disease ,Neurology ,business.industry ,Pill ,Wuzi yanzong ,medicine ,Neurology (clinical) ,Pharmacology ,Signal transduction ,medicine.disease ,business - Published
- 2021
45. Modified spinal cord stimulation (MSCS) promoted to awaken the patients with chronic unconsciousness
- Author
-
J.J. Huang, Guang-Yuan Han, Li-Juan Song, Jie-Zhong Yu, Dong Ma, Yong-Wen Bai, Guo-Qing Zhang, Guo-Tao Zhuang, Ke-Xin Liu, Cun-Gen Ma, J.C. Liu, and Yong Wang
- Subjects
Neurology ,business.industry ,Anesthesia ,Unconsciousness ,Mesenchymal stem cell ,medicine ,Neurology (clinical) ,Spinal cord stimulation ,medicine.symptom ,business - Published
- 2021
46. Hydroxyfasudil ameliorates Parkinson’ s disease possibly through anti-inflammation and neuroprotection
- Author
-
Li-Juan Song, Guo-Guo Chu, Jie-Zhong Yu, H.Z. Zhang, Cun-Gen Ma, Jing Wang, Zhu-Yue Miao, Bao-Guo Xiao, Qing Wang, J.J. Huang, Guang-Yuan Han, and Z. Chai
- Subjects
Parkinson's disease ,Neurology ,business.industry ,medicine ,Anti inflammation ,Neurology (clinical) ,Pharmacology ,medicine.disease ,business ,Neuroprotection - Published
- 2021
47. Neuroprotective effect of hyperoside on MPTP/MPP + -induced PD model
- Author
-
Hui Jie Fan, Xing Jie Xu, Cun Gen Ma, J.J. Huang, Qing Wang, Tao Pan, Jie Zhong Yu, Yan Rong Li, Bao Guo Xiao, Xin Liang Wang, Z. Chai, and Lu Jia
- Subjects
chemistry.chemical_compound ,Neurology ,chemistry ,MPTP ,Hyperoside ,Neurology (clinical) ,Pharmacology ,Neuroprotection - Published
- 2021
48. Safflower yellow (SY) inhibits the ischemia and hypoxia-induced inflammatory signalling transduction in both rats and BV2 cell lines
- Author
-
Z. Chai, Ce Zhang, Qing Wang, Zhi-Bin Ding, Yuqing Yan, Guang-Yuan Han, Xing-Wang Yang, Jie-Zhong Yu, Li-Juan Song, J.J. Huang, Cun-Gen Ma, and Zhu-Yue Miao
- Subjects
Transduction (genetics) ,Signalling ,Neurology ,Cell culture ,Chemistry ,Ischemia ,medicine ,Neurology (clinical) ,Safflower yellow ,Hypoxia (medical) ,medicine.symptom ,medicine.disease ,Cell biology - Published
- 2021
49. Ginkgo K promotes the phagocytosis of myelin debris by astrocytes via rebalancing TLR4 and ABCA1 signaling pathways
- Author
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Qing Wang, Xiao-Hui Li, Bao-Guo Xiao, Guo-Bin Song, Dong Ma, Qiang Miao, Minfang Guo, Ru-Heng Wei, J.J. Huang, Cun-Gen Ma, Li-Juan Song, and J.Z. Yu
- Subjects
biology ,Chemistry ,Ginkgo ,Phagocytosis ,biology.organism_classification ,Cell biology ,Myelin ,medicine.anatomical_structure ,Neurology ,ABCA1 ,medicine ,TLR4 ,biology.protein ,Neurology (clinical) ,Signal transduction - Published
- 2021
50. miR-1908 as a novel prognosis marker of glioma via promoting malignant phenotype and modulating SPRY4/RAF1 axis
- Author
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Yan-Hua Li, Fan Huijie, Ran Zhou, Yanyan Li, Cun-Gen Ma, Zhi Chai, Xiaoming Jin, Li-Juan Song, and Jie-Zhong Yu
- Subjects
0301 basic medicine ,Cancer Research ,SPRY4 ,Cell ,Cell Cycle Proteins ,Nerve Tissue Proteins ,Biology ,Bioinformatics ,miR-1908 ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Glioma ,microRNA ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,RAF1 ,KEGG ,Cell Proliferation ,MiRTarBase ,Oncogene ,Brain Neoplasms ,Intracellular Signaling Peptides and Proteins ,apoptosis ,Articles ,General Medicine ,Cell cycle ,Prognosis ,medicine.disease ,Survival Analysis ,Molecular medicine ,Up-Regulation ,Proto-Oncogene Proteins c-raf ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,prognostic marker - Abstract
MicroRNAs (miRNAs) are reported to be involved in the development of glioma. However, study on miRNAs in glioma is limited. The present study aimed to identify miRNAs which can act as potential novel prognostic markers for glioma and analyze its possible mechanism. We show that miR-1908 correlates with shorter survival time of glioma patients via promoting cell proliferation, invasion, anti-apoptosis and regulating SPRY4/RAF1 axis. Analysis of GEO and TCGA database found that miR-1908 was significantly upregulated in glioma tissues, and strongly associated with shorter survival time of glioma patients. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that miR-1908 is mainly involved in regulating cell proliferation, invasion and apoptosis. To further confirm the above results, in vitro, glioma U251 cells were transfected with miR-1908 mimics or inhibitor, and upregulated miR-1908 promoted U251 cell proliferation, and enhanced the ability of invasion by Transwell assay. In addition, upregulated miR-1908 also enhanced anti-apoptosis ability of U251 cells through decreasing pro-apoptosis protein Bax expression. Since miRNAs regulate numerous biological processes by targeting broad set of messenger RNAs, validated target genes of miR-1908 in glioma were analyzed by TargetScan and miRTarBase databases. Among them SPRY4 was significantly decreased in glioma tissues and associated with short survival time, which was selected as the key target gene of miR-1908. Moreover, protein-protein interaction (PPI) showed that SPRY4 could interacted with pro-oncogene RAF1 and negatively correlated with RAF1 expression. Consistent with above analysis, in vitro, western blot analysis identified that miR-1908 upregulated significantly decreased SPRY4 expression and increased RAF1 expression. Hence, miR-1908 was correlated with poor prognosis of glioma via promoting cell proliferation, invasion, anti-apoptosis and regulating SPRF4/RAF1 axis. Our results elucidated the tumor promoting role of miR-1908 and established miR-1908 as a potential novel prognostic marker for glioma.
- Published
- 2017
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