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  1. Article: Bushen-Huatan-Yizhi formula reduces spatial learning and memory challenges through inhibition of the GSK-3β/CREB pathway in AD-like model rats

    Yang, Shu-Sheng / Shi, He-Yuan / Zeng, Peng / Xia, Jing / Wang, Ping / Lin, Li

    Phytomedicine. 2021 Sept., v. 90

    2021  

    Abstract: There is an increase in cases of Alzheimer's disease (AD) stemming from a globally ageing population demographic. Although substantial research efforts were performed for the scope of prophylaxis and therapeutic measure development against AD, based on ... ...

    Abstract There is an increase in cases of Alzheimer's disease (AD) stemming from a globally ageing population demographic. Although substantial research efforts were performed for the scope of prophylaxis and therapeutic measure development against AD, based on its pathogenesis, most were unsuccessful. Bushen-Huatan-Yizhi formula (BSHTYZ) is extensively implemented to manage dementia. However, few studies have been carried out to understand how BSHTYZ enhances recovery of spatial learning and memory and how it modulates relevant molecular interplays in order to achieve this.To investigate neuroprotective function, ameliorating learning/memory capacity of BSHTYZ via GSK-3β / CREB signaling pathway in rat AD models influenced through Aβ₁₋₄₂.A total of 60 male SD rats (3 months old) were randomized into six groups and treated with 2.6 μg/μl Aβ₁₋₄₂ (5 μl) into the lateral ventricle, though the control group (Con) was administered an equivalent volume of vehicle. Consequently, the rat cohorts were administered either BSHTYZ or donepezil hydrochloride or normal saline, by intragastric administration, for four weeks. Spatial learning / memory were detected through the Morris water maze, and possible mechanisms detected by histomorphological examination and Western blot in the rat AD models induced by Aβ₁₋₄₂.Spatial learning/memory issues were monitored after Aβ₁₋₄₂ infusion in rats. Simultaneously, neuron loss in cornuammonis1 (CA1) / dentate gyrus (DG) within hippocampus region were identified, together with enhanced black granule staining within the hippocampus and hyperphosphorylated tau within Ser202 and Ser396 sites. It was also elucidated that Aβ₁₋₄₂ had the capacity to up-regulate glycogen synthase kinase-3β (GSK-3β) and down-regulate cAMP response element binding protein (CREB). BSHTYZ was found to reverse such molecular interplays.The study suggested BSHTYZ could possibly provide neuroprotective role against learning / memory impairment, which provided a potential therapeutic tool delaying the progression of AD molecular interplays that includes the GSK-3β / CREB signaling pathway.
    Keywords Alzheimer disease ; Western blotting ; disease prevention ; glycogen (starch) synthase ; hippocampus ; intragastric administration ; males ; memory ; memory disorders ; neurons ; neuroprotective effect ; pathogenesis ; rats ; therapeutics
    Language English
    Dates of publication 2021-09
    Publishing place Elsevier GmbH
    Document type Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2021.153624
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Bushen-Huatan-Yizhi formula reduces spatial learning and memory challenges through inhibition of the GSK-3β/CREB pathway in AD-like model rats.

    Yang, Shu-Sheng / Shi, He-Yuan / Zeng, Peng / Xia, Jing / Wang, Ping / Lin, Li

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2021  Volume 90, Page(s) 153624

    Abstract: Background: There is an increase in cases of Alzheimer's disease (AD) stemming from a globally ageing population demographic. Although substantial research efforts were performed for the scope of prophylaxis and therapeutic measure development against ... ...

    Abstract Background: There is an increase in cases of Alzheimer's disease (AD) stemming from a globally ageing population demographic. Although substantial research efforts were performed for the scope of prophylaxis and therapeutic measure development against AD, based on its pathogenesis, most were unsuccessful. Bushen-Huatan-Yizhi formula (BSHTYZ) is extensively implemented to manage dementia. However, few studies have been carried out to understand how BSHTYZ enhances recovery of spatial learning and memory and how it modulates relevant molecular interplays in order to achieve this.
    Purpose: To investigate neuroprotective function, ameliorating learning/memory capacity of BSHTYZ via GSK-3β / CREB signaling pathway in rat AD models influenced through Aβ
    Methods: A total of 60 male SD rats (3 months old) were randomized into six groups and treated with 2.6 μg/μl Aβ
    Results: Spatial learning/memory issues were monitored after Aβ
    Conclusion: The study suggested BSHTYZ could possibly provide neuroprotective role against learning / memory impairment, which provided a potential therapeutic tool delaying the progression of AD molecular interplays that includes the GSK-3β / CREB signaling pathway.
    MeSH term(s) Alzheimer Disease/drug therapy ; Animals ; Cyclic AMP Response Element-Binding Protein/metabolism ; Drugs, Chinese Herbal/pharmacology ; Glycogen Synthase Kinase 3 beta/metabolism ; Hippocampus/metabolism ; Male ; Maze Learning ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; tau Proteins/metabolism
    Chemical Substances Creb1 protein, rat ; Cyclic AMP Response Element-Binding Protein ; Drugs, Chinese Herbal ; tau Proteins ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, rat (EC 2.7.11.1)
    Language English
    Publishing date 2021-06-15
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2021.153624
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Protective effects of Da-cheng-qi decoction in rats with intracerebral hemorrhage.

    Zeng, Peng / Wang, Xiao-Ming / Su, Hong-Fei / Zhang, Teng / Ning, Lin-Na / Shi, Yan / Yang, Shu-Sheng / Lin, Li / Tian, Qing

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2021  Volume 90, Page(s) 153630

    Abstract: Background: Intracerebral hemorrhage (ICH), the most fatal subtype of stroke, has no disease-modifying treatment. Da-cheng-qi decoction (DCQ), composed of rhubarb, is one of the most commonly used Chinese traditional decoctions in ICH treatment. But the ...

    Abstract Background: Intracerebral hemorrhage (ICH), the most fatal subtype of stroke, has no disease-modifying treatment. Da-cheng-qi decoction (DCQ), composed of rhubarb, is one of the most commonly used Chinese traditional decoctions in ICH treatment. But the mechanism is not clear. Emodin is an active compound found in rhubarb.
    Purpose: To study the protective effects of DCQ on ICH and its possible mechanisms of action.
    Methods: The ICH model was reproduced by injecting collagenase-VII into the left caudate putamen (CPu) of rats. DCQ and emodin were used to treat the ICH rats for 7 days. Behavior tests, proteomic analysis, morphological studies, and western blotting were performed.
    Results: The neurological deficits in the ICH rats recovered with DCQ and emodin on the 14
    Conclusion: The protective effects of DCQ on ICH were confirmed in this study, and its mechanism may be related to the inhibition of MAPK and activation of M2 microglia. These results are beneficial to the development of ICH therapeutic targets.
    MeSH term(s) Animals ; Cerebral Hemorrhage/drug therapy ; Drugs, Chinese Herbal/pharmacology ; Emodin/pharmacology ; Hippocampus/drug effects ; Proteomics ; Rats ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
    Chemical Substances Da-Cheng-Qi ; Drugs, Chinese Herbal ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Emodin (KA46RNI6HN)
    Language English
    Publishing date 2021-06-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2021.153630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Protective effects of Da-cheng-qi decoction in rats with intracerebral hemorrhage

    Zeng, Peng / Wang, Xiao-Ming / Su, Hong-Fei / Zhang, Teng / Ning, Lin-Na / Shi, Yan / Yang, Shu-Sheng / Lin, Li / Tian, Qing

    Phytomedicine. 2021 Sept., v. 90

    2021  

    Abstract: Intracerebral hemorrhage (ICH), the most fatal subtype of stroke, has no disease-modifying treatment. Da-cheng-qi decoction (DCQ), composed of rhubarb, is one of the most commonly used Chinese traditional decoctions in ICH treatment. But the mechanism is ...

    Abstract Intracerebral hemorrhage (ICH), the most fatal subtype of stroke, has no disease-modifying treatment. Da-cheng-qi decoction (DCQ), composed of rhubarb, is one of the most commonly used Chinese traditional decoctions in ICH treatment. But the mechanism is not clear. Emodin is an active compound found in rhubarb.To study the protective effects of DCQ on ICH and its possible mechanisms of action.The ICH model was reproduced by injecting collagenase-VII into the left caudate putamen (CPu) of rats. DCQ and emodin were used to treat the ICH rats for 7 days. Behavior tests, proteomic analysis, morphological studies, and western blotting were performed.The neurological deficits in the ICH rats recovered with DCQ and emodin on the 14ᵗʰ day after ICH. The proteomics data revealed that DCQ significantly corrected the pathological signals in the CPu and hippocampus after ICH. The numbers of amoebic microglia in the CPu and M2 microglia in both CPu and hippocampus were significantly increased after DCQ and emodin treatment. The increase in GluN2B-containing NMDA receptor (NR2B) and postsynaptic density protein-95, activation of mitogen-activated protein kinase (MAPK) signals in the CPu, and secondary neurodegeneration (SND) in the hippocampus were significantly recovered in DCQ-treated rats. Inhibition of MAPK p38 (p38) in the hippocampus was observed after DCQ and emodin treatment.The protective effects of DCQ on ICH were confirmed in this study, and its mechanism may be related to the inhibition of MAPK and activation of M2 microglia. These results are beneficial to the development of ICH therapeutic targets.
    Keywords active ingredients ; emodin ; hemorrhage ; hippocampus ; mitogen-activated protein kinase ; models ; neurodegenerative diseases ; neuroglia ; proteomics ; rhubarb ; stroke ; therapeutics
    Language English
    Dates of publication 2021-09
    Publishing place Elsevier GmbH
    Document type Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2021.153630
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Melatonin in Alzheimer's disease.

    Lin, Li / Huang, Qiong-Xia / Yang, Shu-Sheng / Chu, Jiang / Wang, Jian-Zhi / Tian, Qing

    International journal of molecular sciences

    2013  Volume 14, Issue 7, Page(s) 14575–14593

    Abstract: Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the ... ...

    Abstract Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.
    MeSH term(s) Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Humans ; Melatonin/metabolism ; Phosphorylation ; tau Proteins/metabolism
    Chemical Substances Amyloid beta-Peptides ; tau Proteins ; Melatonin (JL5DK93RCL)
    Language English
    Publishing date 2013-07-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1661-6596
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms140714575
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  6. Article ; Online: Endoplasmic reticulum stress induces spatial memory deficits by activating GSK-3.

    Lin, Li / Cao, Jie / Yang, Shu-Sheng / Fu, Zheng-Qi / Zeng, Peng / Chu, Jiang / Ning, Lin-Na / Zhang, Teng / Shi, Yan / Tian, Qing / Zhou, Xin-Wen / Wang, Jian-Zhi

    Journal of cellular and molecular medicine

    2018  Volume 22, Issue 7, Page(s) 3489–3502

    Abstract: Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the ... ...

    Abstract Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol-requiring enzyme-1 (IRE-1) and activating transcription factor-6 (ATF-6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats. After TM treatment, GSK-3β was activated and phosphorylation of cAMP response element binding protein at Ser129 (pS129-CREB) was increased with an increased nuclear co-localization of pY126-GSK-3β and pS129-CREB. Simultaneous inhibition of GSK-3β by hippocampal infusion of SB216763 (SB) attenuated TM-induced UPR and spatial memory impairment with restoration of pS129-CREB and synaptic plasticity. We concluded that UPR induces AD-like spatial memory deficits with mechanisms involving GSK-3β/pS129-CREB pathway.
    MeSH term(s) Activating Transcription Factor 6/metabolism ; Alzheimer Disease/pathology ; Animals ; Brain/drug effects ; Brain/pathology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Glycogen Synthase Kinase 3/metabolism ; Male ; Membrane Proteins/metabolism ; Phosphorylation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; Rats, Sprague-Dawley ; Serine/metabolism ; Spatial Memory/drug effects ; Spatial Memory/physiology ; Tunicamycin/toxicity ; Tyrosine/metabolism ; Unfolded Protein Response/drug effects ; eIF-2 Kinase/metabolism
    Chemical Substances Activating Transcription Factor 6 ; Atf6 protein, rat ; Creb1 protein, rat ; Cyclic AMP Response Element-Binding Protein ; Membrane Proteins ; Tunicamycin (11089-65-9) ; Tyrosine (42HK56048U) ; Serine (452VLY9402) ; Ern2 protein, rat (EC 2.7.1.-) ; PERK kinase (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Language English
    Publishing date 2018-04-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.13626
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  7. Article ; Online: Region-specific expression of tau, amyloid-β protein precursor, and synaptic proteins at physiological condition or under endoplasmic reticulum stress in rats.

    Lin, Li / Yang, Shu-Sheng / Chu, Jiang / Wang, Lu / Ning, Lin-Na / Zhang, Teng / Jiang, Qian / Tian, Qing / Wang, Jian-Zhi

    Journal of Alzheimer's disease : JAD

    2014  Volume 41, Issue 4, Page(s) 1149–1163

    Abstract: Region-specific neurodegeneration was reported in brains of Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we studied the expression of some AD-associated proteins in temporal cortex, frontal cortex, cerebellum, and ... ...

    Abstract Region-specific neurodegeneration was reported in brains of Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we studied the expression of some AD-associated proteins in temporal cortex, frontal cortex, cerebellum, and hippocampus of 4-month-old male Sprague-Dawley rats. Levels of the phosphorylated tau at Thr231, Ser396, and Ser202/Thr205, phosphorylated amyloid-β protein precursor (AβPP) and amyloid-β, synapse-associated proteins glutamate receptors 2, N-methyl-D-aspartic receptors 1 (NR1), NR2A, NR2B, and postsynaptic density protein 95 were much lower in cerebellum, while the levels of total tau, phosphorylated tau at Thr205, Ser214, Ser262, and Ser198/199/202 epitopes, and total AβPP were similar in the four brain regions. As endoplasmic reticulum (ER) stress was reported in the early stage of AD, we injected tunicamycin, an ER stress inducer, into the lateral ventricular of rats and 48 hours later found in the other three brain regions but not cerebellum, increasing of binding immunoglobulin protein with the increased phosphorylation of pancreatic ER kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Simultaneously, levels of phosphorylated tau at all of the above sites were significantly increased with the activation of glycogen synthase kinase-3β in temporal cortex, frontal cortex, and/or hippocampus, but not cerebellum. The synapse-associated proteins, GluR2, PSD95, and synapsin1, were found decreased in the hippocampus after tunicamycin exposure. These data together may partially explain why the AD-like neuropathology, such as formation of neurofibrillary tangles, was rarely detected in cerebellum.
    MeSH term(s) Amyloid beta-Protein Precursor/metabolism ; Analysis of Variance ; Animals ; Brain/drug effects ; Brain/metabolism ; Disks Large Homolog 4 Protein ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Enzyme-Linked Immunosorbent Assay ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Membrane Proteins/metabolism ; Neurofibrillary Tangles/metabolism ; Neurofibrillary Tangles/pathology ; Phosphorylation/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate/metabolism ; Synapses/drug effects ; Synapses/metabolism ; Synapsins/metabolism ; Tunicamycin/pharmacology ; tau Proteins/metabolism
    Chemical Substances Amyloid beta-Protein Precursor ; Disks Large Homolog 4 Protein ; Dlg4 protein, rat ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Receptors, Glutamate ; Synapsins ; tau Proteins ; Tunicamycin (11089-65-9)
    Language English
    Publishing date 2014
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-140207
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  8. Article ; Online: High Morphologic Plasticity of Microglia/Macrophages Following Experimental Intracerebral Hemorrhage in Rats.

    Yang, Shu-Sheng / Lin, Li / Liu, Yue / Wang, Jie / Chu, Jiang / Zhang, Teng / Ning, Lin-Na / Shi, Yan / Fang, Ying-Yan / Zeng, Peng / Wang, Jian-Zhi / Qiu, Ming-Yi / Tian, Qing

    International journal of molecular sciences

    2016  Volume 17, Issue 7

    Abstract: As current efforts have limited effects on the clinical outcome of intracerebral hemorrhage (ICH), the mechanisms including microglia/macrophages that involved inflammation need further investigation. Here, 0.4 units of collagenase VII were injected into ...

    Abstract As current efforts have limited effects on the clinical outcome of intracerebral hemorrhage (ICH), the mechanisms including microglia/macrophages that involved inflammation need further investigation. Here, 0.4 units of collagenase VII were injected into the left caudate putamen (CPu) to duplicate ICH rat models. In the brains of ICH rats, microglia/macrophages, the nearest cells to the hemorrhagic center, were observed as ameboid and Prussian-blue positive. Furthermore, the ameboid microglia/macrophages were differentiation (CD) 68 and interleukin-1β (IL-1β) positive, and neither CD206 nor chitinase3-like 3 (Ym1) positive, suggesting their strong abilities of phagocytosis and secretion of IL-1β. According to the distance to the hemorrhagic center, we selected four areas-I, II, III, and IV-to analyze the morphology of microglia/macrophages. The processes decreased successively from region I to region IV. Microglia/macrophages in region IV had no processes. The processes in region I were radially distributed, however, they showed obvious directivity towards the hemorrhagic center in regions II and III. Region III had the largest density of compactly arrayed microglia/macrophages. All these in vivo results present the high morphologic plasticity of microglia/macrophages and their functions in the pathogenesis of ICHs.
    MeSH term(s) Animals ; Behavior, Animal ; Cerebral Hemorrhage/complications ; Cerebral Hemorrhage/physiopathology ; Fluorescent Antibody Technique ; Immunohistochemistry ; Macrophages/pathology ; Magnetic Resonance Imaging ; Male ; Microglia/pathology ; Neuronal Plasticity/physiology ; Rats ; Rats, Sprague-Dawley
    Language English
    Publishing date 2016-07-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms17071181
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  9. Article ; Online: SIL1 Rescued Bip Elevation-Related Tau Hyperphosphorylation in ER Stress.

    Liu, Zan-Chao / Chu, Jiang / Lin, Li / Song, Jie / Ning, Lin-Na / Luo, Hong-Bin / Yang, Shu-Sheng / Shi, Yan / Wang, Qun / Qu, Na / Zhang, Qi / Wang, Jian-Zhi / Tian, Qing

    Molecular neurobiology

    2015  Volume 53, Issue 2, Page(s) 983–994

    Abstract: Endoplasmic reticulum (ER) stress has been indicated in the early stage of Alzheimer's disease (AD), in which tau hyperphosphorylation is one major pathological alteration. The elevation of binding immunoglobulin protein (Bip), an important ER chaperon, ... ...

    Abstract Endoplasmic reticulum (ER) stress has been indicated in the early stage of Alzheimer's disease (AD), in which tau hyperphosphorylation is one major pathological alteration. The elevation of binding immunoglobulin protein (Bip), an important ER chaperon, was reported in AD brain. It is important to study the roles of ER-related chaperons in tau hyperphosphorylation. In this research, increased Bip was found in the brains of the AD model mice (Tg2576) compared to the age-matched control mice. Meanwhile, deficiency of SIL1, an important co-chaperon of Bip, was observed in brains of Tg2576 mice and in ER stress both in vivo and in vitro. Then, we transfected Bip-EGFP plasmid into HEK293 cells stably expressing the longest human tau (HEK293/tau) or N2a cells and found that increased Bip induced tau hyperphosphorylation via activating glycogen synthase kinase-3β (GSK-3β), an important tau kinase, and increased the association with tau and GSK-3β. When we overexpressed SIL1 in Bip-transfected HEK293/tau cells and thapsigargin-treated HEK293/tau cells, significantly reduced tau hyperphosphorylation and GSK-3β activation were observed. These results suggested the important roles of ER-related chaperons, Bip and SIL1, in AD-like tau hyperphosphorylation.
    MeSH term(s) Animals ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Endoplasmic Reticulum Stress/drug effects ; Enzyme Activation/drug effects ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Guanine Nucleotide Exchange Factors/metabolism ; HEK293 Cells ; Heat-Shock Proteins/metabolism ; Humans ; Indoles/pharmacology ; Maleimides/pharmacology ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Biological ; Phosphorylation/drug effects ; Rats, Sprague-Dawley ; Thapsigargin/pharmacology ; tau Proteins/metabolism
    Chemical Substances Guanine Nucleotide Exchange Factors ; Heat-Shock Proteins ; Indoles ; Maleimides ; SB 216763 ; SIL1 protein, mouse ; tau Proteins ; Thapsigargin (67526-95-8) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; molecular chaperone GRP78 (YCYIS6GADR)
    Language English
    Publishing date 2015-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-014-9039-4
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  10. Article: Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008.

    Wang, Hong-xiu / Yue, Jun / Han, Min / Yang, Jing-hui / Gao, Rong-liang / Jing, Ling-jie / Yang, Shu-sheng / Zhao, Yan-lin

    Chinese medical journal

    2010  Volume 123, Issue 2, Page(s) 184–187

    Abstract: Background: An increasing incidence of disease caused by nontuberculous mycobacteria (NTM) is being reported. The purpose of this study was to determine the isolation rates of NTM from various clinical specimens, and their antimicrobial susceptibility ... ...

    Abstract Background: An increasing incidence of disease caused by nontuberculous mycobacteria (NTM) is being reported. The purpose of this study was to determine the isolation rates of NTM from various clinical specimens, and their antimicrobial susceptibility patterns, over a 4-year period in Shanghai.
    Methods: All NTM isolated between 2005 and 2008 at Shanghai Pulmonary Hospital, a key laboratory of mycobacteria tuberculosis in Shanghai, China, were identified with conventional biochemical tests and 16S rRNA gene sequencing. Antimicrobial susceptibility for all NTM was determined using the BACTEC MGIT 960 system.
    Results: A total of 21,221 specimens were cultured, of which 4868 (22.94%) grew acid fast bacilli (AFB), and 248 (5.09%) of the AFB were NTM. The prevalence rate of NTM was determined as 4.26%, 4.70%, 4.96% and 6.38% among mycobacteria culture positive samples in years 2005, 2006, 2007 and 2008 respectively. These data indicated that the prevalence rate has continuously increased. Sixteen different species of NTM were identified, the most commonly encountered NTM in Shanghai were M. chelonae (26.7%), followed by M. fortuitum (15.4%), M. kansasii (14.2%), M. avium-intracellulare complex (13.1%) and M. terrae (6.9%). The rare species identified were M. marinum, M. gastri, M. triviale, M. ulcerans, M. smegmatis, M. phlci, M. gordonae, M. szulgai, M. simiae, M. scrofulaceum and M. xenopi. The five most commonly identified NTM species showed high drug resistance to general anti-tuberculosis drugs, particularly, M. chelonae and M. fortuitum appear to be multi-drug resistance.
    Conclusions: The prevalence of NTM in Shanghai showed a tendency to increase over the course of the study. The five most commonly isolated NTM species showed high drug resistance to first line anti-tuberculosis drugs.
    MeSH term(s) Antitubercular Agents/pharmacology ; China/epidemiology ; Drug Resistance, Bacterial ; Mycobacterium/drug effects ; Mycobacterium/physiology ; Mycobacterium Infections/epidemiology ; Mycobacterium Infections/microbiology ; Mycobacterium chelonae/drug effects ; Mycobacterium chelonae/physiology ; Mycobacterium fortuitum/drug effects ; Mycobacterium fortuitum/physiology ; Mycobacterium kansasii/drug effects ; Mycobacterium kansasii/physiology ; Mycobacterium marinum/drug effects ; Mycobacterium marinum/physiology ; Mycobacterium xenopi/drug effects ; Mycobacterium xenopi/physiology ; Nontuberculous Mycobacteria/drug effects ; Nontuberculous Mycobacteria/physiology ; Prevalence
    Chemical Substances Antitubercular Agents
    Language English
    Publishing date 2010-01-20
    Publishing country China
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 127089-8
    ISSN 0366-6999 ; 1002-0187
    ISSN 0366-6999 ; 1002-0187
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