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  1. Article ; Online: Mendelian Randomization Identifies Genetically Supported Drug Targets for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

    Zhu, Yahui / Li, Mao / Wang, Hongfen / Yang, Fei / Du, RongRong / Pang, Xinyuan / Bai, Jiongming / Huang, Xusheng

    Molecular neurobiology

    2023  

    Abstract: Currently, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have no effective treatments. Drug repurposing offers a rapid method to meet therapeutic need for ALS and FTD. To identify therapeutic targets associated with ALS and FTD, ... ...

    Abstract Currently, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have no effective treatments. Drug repurposing offers a rapid method to meet therapeutic need for ALS and FTD. To identify therapeutic targets associated with ALS and FTD, Mendelian randomization (MR) analysis and colocalization were performed. Genetic instruments were based on transcriptomic and proteomic data for 422 actionable proteins targeted by approved drugs or clinical drug candidates. The publicly available ALS GWAS summary data (including a total of 20,806 ALS cases and 59,804 controls) and FTD GWAS summary data (including a total of 2154 patients with FTD and 4308 controls) were used. Using cis-expression quantitative trait loci and cis-protein quantitative trait loci genetic instruments, we identified several drug targets for repurposing (ALS: MARK3, false-discovery rate (FDR) = 0.043; LTBR, FDR = 0.068) (FTD: HLA-DRB1, FDR = 0.083; ADH5, FDR = 0.056). Our MR study analyzed the actionable druggable proteins and provided potential therapeutic targets for ALS and FTD. Future studies should further elucidate the underlying mechanism of corresponding drug targets in the pathogenesis of ALS and FTD.
    Language English
    Publishing date 2023-11-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-023-03817-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2411: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

    Du, Rong-Rong / Zhou, Ji-Chao / Qin, Wen-Jie / Lu, Kai-Zhou / Duan, Xiu-Mei / Yang, Ya-Nan / Yuan, Xiang / Li, Kun / Zhang, Xiao-Wei / Zhang, Pei-Cheng

    Bioorganic chemistry

    2024  Volume 143, Page(s) 107079

    Abstract: Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were ... ...

    Abstract Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.
    MeSH term(s) Glycosides/pharmacology ; Glycosides/chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Roots/chemistry ; Benzofurans/chemistry ; Benzofurans/pharmacology
    Chemical Substances Glycosides ; Benzofurans
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120080-x
    ISSN 1090-2120 ; 0045-2068
    ISSN (online) 1090-2120
    ISSN 0045-2068
    DOI 10.1016/j.bioorg.2023.107079
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    Zs.A 4207: Show issues Location:
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  3. Article ; Online: Engineering of an enhanced synthetic Notch receptor by reducing ligand-independent activation.

    Yang, Zi-Jie / Yu, Zi-Yan / Cai, Yi-Ming / Du, Rong-Rong / Cai, Liang

    Communications biology

    2020  Volume 3, Issue 1, Page(s) 116

    Abstract: Notch signaling is highly conserved in most animals and plays critical roles during neurogenesis as well as embryonic development. Synthetic Notch-based systems, modeled from Notch receptors, have been developed to sense and respond to a specific ... ...

    Abstract Notch signaling is highly conserved in most animals and plays critical roles during neurogenesis as well as embryonic development. Synthetic Notch-based systems, modeled from Notch receptors, have been developed to sense and respond to a specific extracellular signal. Recent advancement of synNotch has shown promise for future use in cellular engineering to treat cancers. However, synNotch from Morsut et al. (2016) has a high level of ligand-independent activation, which limits its application. Here we show that adding an intracellular hydrophobic sequence (QHGQLWF, named as RAM7) present in native Notch, significantly reduced ligand-independent activation. Our enhanced synthetic Notch receptor (esNotch) demonstrates up to a 14.6-fold reduction in ligand-independent activation, without affecting its antigen-induced activation efficiency. Our work improves a previously reported transmembrane receptor and provides a powerful tool to develop better transmembrane signaling transduction modules for further advancement of eukaryotic synthetic biology.
    MeSH term(s) Amino Acid Sequence ; Antigens/metabolism ; Cell Engineering/methods ; Cell Membrane/metabolism ; Cloning, Molecular/methods ; HEK293 Cells ; Humans ; Ligands ; Plasmids/genetics ; Protein Domains ; Proteolysis ; Receptors, Artificial/chemistry ; Receptors, Artificial/metabolism ; Receptors, Notch/chemistry ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction/genetics ; Single-Chain Antibodies ; Synthetic Biology/methods ; Transfection
    Chemical Substances Antigens ; Ligands ; Receptors, Artificial ; Receptors, Notch ; Single-Chain Antibodies
    Language English
    Publishing date 2020-03-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-020-0848-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China.

    Huang, Xiao-Feng / Wang, Kai-Yue / Liang, Zhan-Hua / Du, Rong-Rong / Zhou, Li-Na

    European neurology

    2015  Volume 73, Issue 5-6, Page(s) 337–341

    Abstract: Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm.: Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face- ... ...

    Abstract Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm.
    Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families.
    Results: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients.
    Conclusions: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.
    MeSH term(s) Adult ; Aged ; Blepharospasm/diagnosis ; Blepharospasm/drug therapy ; Botulinum Toxins, Type A/therapeutic use ; China ; Diagnosis, Differential ; Dry Eye Syndromes/diagnosis ; Female ; Humans ; Keratoconjunctivitis/diagnosis ; Male ; Middle Aged ; Myasthenia Gravis/diagnosis ; Neuromuscular Agents/therapeutic use ; Retrospective Studies
    Chemical Substances Neuromuscular Agents ; Botulinum Toxins, Type A (EC 3.4.24.69)
    Language English
    Publishing date 2015-05-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209426-5
    ISSN 1421-9913 ; 0014-3022
    ISSN (online) 1421-9913
    ISSN 0014-3022
    DOI 10.1159/000381707
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 575: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China

    Huang, Xiao-Feng / Wang, Kai-Yue / Liang, Zhan-Hua / Du, Rong-Rong / Zhou, Li-Na

    European Neurology

    2015  Volume 73, Issue 5-6, Page(s) 337–341

    Abstract: Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to- ... ...

    Institution Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian Department of Neurology, Linyi City People's Hospital, Linyi and Department of Neurology, First Affiliated Hospital of Baotou Medical College, Baotou, China
    Abstract Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. Results: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. Conclusions: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.
    Keywords Focal dystonia ; Blepharospasm ; Dry eyes ; Photophobia ; Myasthenia gravis ; Botulinum toxin
    Language English
    Publishing date 2015-05-19
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Original Paper
    ZDB-ID 209426-5
    ISSN 1421-9913 ; 0014-3022
    ISSN (online) 1421-9913
    ISSN 0014-3022
    DOI 10.1159/000381707
    Database Karger publisher's database

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 575: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China

    Huang, Xiao-Feng / Wang, Kai-Yue / Liang, Zhan-Hua / Du, Rong-Rong / Zhou, Li-Na

    European Neurology

    2015  Volume 73, Issue 5-6, Page(s) 337–341

    Abstract: Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to- ... ...

    Abstract Purpose: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. Methods: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. Results: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. Conclusions: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.© 2015 S. Karger AG, Basel
    Keywords Focal dystonia ; Blepharospasm ; Dry eyes ; Photophobia ; Myasthenia gravis ; Botulinum toxin
    Language English
    Publisher S. Karger AG
    Publishing place Basel
    Publishing country Switzerland
    Document type Article ; Online
    ZDB-ID 209426-5
    ISSN 1421-9913 ; 0014-3022 ; 0014-3022
    ISSN (online) 1421-9913
    ISSN 0014-3022
    DOI 10.1159/000381707
    Database Karger publisher's database

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 575: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    ab Jg. 2022: Lesesaal (EG)

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