9 results on '"Qing-Xian Han"'
Search Results
2. The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice
- Author
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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
- Subjects
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
3. Fasudil-Triggered Phagocytosis of Myelin Debris Promoted Meylin Regeneration via the Activation of TREM2/DAP12 Signaling Pathway in Cuprizone-Induced Mice
- Author
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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.
- Published
- 2021
4. Ethyl Pyruvate–Derived Transdifferentiation of Astrocytes to Oligodendrogenesis in Cuprizone-Induced Demyelinating Model
- Author
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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
- Subjects
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.
- Published
- 2020
5. Fasudil enhances the phagocytosis of myelin debris and the expression of neurotrophic factors in cuprizone-induced demyelinating mice
- Author
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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
- Subjects
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.
- Published
- 2020
6. 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
7. Fasudil promoted remyelination in CPZ-induced mice by regulating the function of astrocytes
- Author
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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
8. Temporal and spatial evolution of various functional neurons during demyelination induced by cuprizone.
- Author
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Jun An, Yan He, Jun-Jun Yin, Zhi-Bin Ding, Qing-Xian Han, Yang-Yang Chen, Qing Wang, Zhi Chai, Jie-Zhong Yu, Li-Juan Song, Bao-Guo Xiao, and Cun-Gen Ma
- Abstract
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Here we report the temporal and spatial evolution of various functional neurons during demyelination in a cuprizone (CPZ)-induced mouse model. CPZ did not significantly induce the damage of axons and neurons after 2 wk of feeding. However, after 4-6 wk of CPZ feeding, axons and neurons were markedly reduced in the cortex, posterior thalamic nuclear group, and hippocampus. Simultaneously, the expression of TPH
+ tryptophan neurons and VGLUT1+ glutamate neurons was obviously decreased, and the expression of TH+ dopaminergic neurons was slightly decreased in the tail part of the substantia nigra striatum, whereas the number of ChAT+ cholinergic neurons was not significantly different in the brain. In the second week of feeding, CPZ caused a higher level of glutamate secretion and upregulated the expression of EAAT2 on astrocytes, which should contribute to rapid and sufficient glutamate uptake and removal. This finding reveals that astrocyte-driven glutamate reuptake protected the CNS from excitotoxicity by rapid reuptake of glutamate in 4-6 wk of CPZ feeding. At this stage, although NG2+ oligodendroglia progenitor cells (OPCs) were enhanced in the demyelination foci, the myelin sheath was still absent. In conclusion, we comprehensively observed the temporal and spatial evolution of various functional neurons. Our results will assist with understanding how demyelination affects neurons during CPZ-induced demyelination and provide novel information for neuroprotection in myelin regeneration and demyelinating diseases. NEW & NOTEWORTHY Our results further indicate temporal and spatial evolution of various functional neurons during the demyelination in a cuprizone (CPZ)-induced mouse model, which mainly occur 4-6 wk after CPZ feeding. At the same time, the axonal compartment is damaged and, consequently, neuronal death occurs, while glutamate neurons are lost obviously. The astrocyte-mediated glutamate reuptake could protect the neurons from the excitatory effects of glutamate. [ABSTRACT FROM AUTHOR]- Published
- 2021
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9. Ethyl pyruvate enhances spontaneous remyelination by targeting microglia phagocytosis
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Qing Wang, Cun-Gen Ma, Qing-Xian Han, Qiang Miao, Jun An, Zhi-Bin Ding, Yan He, Jun-Jun Yin, Bao-Guo Xiao, and Ruo-Xuan Sui
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0301 basic medicine ,Male ,Programmed cell death ,Multiple Sclerosis ,Cell Survival ,Phagocytosis ,Immunology ,Cell Line ,03 medical and health sciences ,Myelin ,Cuprizone ,0302 clinical medicine ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Remyelination ,Pyruvates ,Neuroinflammation ,Pharmacology ,Microglia ,Behavior, Animal ,Chemistry ,Cell growth ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,030220 oncology & carcinogenesis ,TLR4 ,Cytokines ,Demyelinating Diseases - Abstract
Ethyl pyruvate (EP), a simple derivative of the endogenous energy substrate pyruvate, provides strong anti-inflammatory and anti-oxidative properties. but its role in remyelination has not been explored. In this study, EP efficiently improved the behavioural performance and histological demyelination in cuprizone (CPZ)-induced mouse model. In terms of action, EP treatment enhanced microglia migration, increased the phagocytosis of myelin debris by BV2 microglia and primary microglia, induced cell proliferation and subsequent cell death. At the same time, EP induced microglia to exhibit M2 phenotype, representing decreased iNOS/TNF-α and increased Arg-1/IL-10. In addition, EP decreased microglia enrichment in myelin sheath, and declined TLR4/p-NF-kb/p65 and IL-1β and IL-6, inhibiting microglia-mediated neuroinflammation. As a result, EP treatment promoted the generation of oligodendrocyte progenitor cells (OPCs) and the differentiation from maturation to mature oligodendrocytes, which may be related to the up-regulation of Sox2. Given these data, we provided the proof-of-experiment that EP should be beneficial in multiple sclerosis or demyelinating lesions. However, further studies on the possibility to use EP as therapeutic application are warranted.
- Published
- 2019
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