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  1. Article ; Online: LcSAO1, an Unconventional DOXB Clade 2OGD Enzyme from Ligusticum chuanxiong Catalyzes the Biosynthesis of Plant-Derived Natural Medicine Butylphthalide

    Xueqing Chen / Xiaopeng Zhang / Wenkai Sun / Zhuangwei Hou / Bao Nie / Fengjiao Wang / Song Yang / Shourui Feng / Wei Li / Li Wang

    International Journal of Molecular Sciences, Vol 24, Iss 24, p

    2023  Volume 17417

    Abstract: ... botanical remedy Ligusticum chuanxiong . While chemical synthesis offers a viable route, limitations ... various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching ... transcriptome data from different tissues of L. chuanxiong , we identified four rhizome-specific genes annotated ...

    Abstract Butylphthalide, a prescription medicine recognized for its efficacy in treating ischemic strokes approved by the State Food and Drug Administration of China in 2005, is sourced from the traditional botanical remedy Ligusticum chuanxiong . While chemical synthesis offers a viable route, limitations in the production of isomeric variants with compromised bioactivity necessitate alternative strategies. Addressing this issue, biosynthesis offers a promising solution. However, the intricate in vivo pathway for butylphthalide biosynthesis remains elusive. In this study, we examined the distribution of butylphthalide across various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching transcriptome data from different tissues of L. chuanxiong , we identified four rhizome-specific genes annotated as 2-oxoglutarate-dependent dioxygenase (2-OGDs) that emerged as promising candidates involved in butylphthalide biosynthesis. Among them, LcSAO1 demonstrates the ability to catalyze the desaturation of senkyunolide A at the C-4 and C-5 positions, yielding the production of butylphthalide. Experimental validation through transient expression assays in Nicotiana benthamiana corroborates this transformative enzymatic activity. Notably, phylogenetic analysis of LcSAO1 revealed that it belongs to the DOXB clade, which typically encompasses genes with hydroxylation activity, rather than desaturation. Further structure modelling and site-directed mutagenesis highlighted the critical roles of three amino acid residues, T98, S176, and T178, in substrate binding and enzyme activity. By unraveling the intricacies of the senkyunolide A desaturase, the penultimate step in the butylphthalide biosynthesis cascade, our findings illuminate novel avenues for advancing synthetic biology research in the realm of medicinal natural products.
    Keywords butylphthalide ; desaturation ; Fe (II)/2-oxoglutarate-dependent dioxygenase ; Ligusticum chuanxiong ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Book ; Online ; Thesis: Topography-matching heteromultivalent nanoparticles for influenza A virus inhibition

    Nie, Chuanxiong [Verfasser]

    2020  

    Author's details Chuanxiong Nie
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Freie Universität Berlin
    Publishing place Berlin
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article ; Online: Correction to "Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures".

    Pouyan, Paria / Nie, Chuanxiong / Bhatia, Sumati / Wedepohl, Stefanie / Achazi, Katharina / Osterrieder, Nikolaus / Haag, Rainer

    Biomacromolecules

    2021  Volume 22, Issue 5, Page(s) 2298

    Language English
    Publishing date 2021-04-23
    Publishing country United States
    Document type Published Erratum
    ISSN 1526-4602
    ISSN (online) 1526-4602
    DOI 10.1021/acs.biomac.1c00483
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Charge Matters: Mutations in Omicron Variant Favor Binding to Cells.

    Nie, Chuanxiong / Sahoo, Anil Kumar / Netz, Roland R / Herrmann, Andreas / Ballauff, Matthias / Haag, Rainer

    Chembiochem : a European journal of chemical biology

    2022  Volume 23, Issue 6, Page(s) e202100681

    Abstract: Evidence is strengthening to suggest that the novel SARS-CoV-2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although the mutations in the spike protein are known, the molecular basis for why the additional ... ...

    Abstract Evidence is strengthening to suggest that the novel SARS-CoV-2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although the mutations in the spike protein are known, the molecular basis for why the additional mutations in the spike protein that have not previously occurred account for Omicron's higher infection potential, is not understood. We propose, based on chemical rational and molecular dynamics simulations, that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs. wild type) increases binding to cellular polyanionic receptors, such as heparan sulfate due to multivalent charge-charge interactions. This observation is a starting point for targeted drug development.
    MeSH term(s) COVID-19/virology ; Humans ; Mutation ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-02-02
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202100681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A fast open-source Fiji-macro to quantify virus infection and transfection on single-cell level by fluorescence microscopy

    Yannic Kerkhoff / Stefanie Wedepohl / Chuanxiong Nie / Vahid Ahmadi / Rainer Haag / Stephan Block

    MethodsX, Vol 9, Iss , Pp 101834- (2022)

    2022  

    Abstract: The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy ... ...

    Abstract The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy images with single-cell resolution. The macro presented here was validated by successful reconstruction of fluorescent and non-fluorescent cell mixing ratios (for fluorescence fractions ranging between 0 and 100%) and applied to quantify the efficiency of transfection and virus infection inhibition. It performed well compared with manually obtained image quantification data. Its use is not limited to the cases shown here but is applicable for most monolayered cellular assays with nuclei staining. We provide a detailed description of how the macro works and how it is applied to image data. It can be downloaded free of charge and may be used by and modified according to the needs of the user.• Rapid, simple, and reproducible segmentation of eukaryotic cells in confluent cellular assays• Open-source software for use without technical or computational expertise• Single-cell analysis allows identification and quantification of virus infected cell populations and infection inhibition
    Keywords Single-cell fluorescence quantification (SCFQ) macro ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Well-Defined Nanostructured Biointerfaces: Strengthened Cellular Interaction for Circulating Tumor Cells Isolation.

    Yu, Leixiao / Tang, Peng / Nie, Chuanxiong / Hou, Yong / Haag, Rainer

    Advanced healthcare materials

    2021  Volume 10, Issue 11, Page(s) e2002202

    Abstract: The topographic features at the cell-material biointerface are critical for cellular sensing of the extracellular environment (ECM) and have gradually been recognized as key factors that regulate cell adhesion behavior. Herein, a well-defined ... ...

    Abstract The topographic features at the cell-material biointerface are critical for cellular sensing of the extracellular environment (ECM) and have gradually been recognized as key factors that regulate cell adhesion behavior. Herein, a well-defined nanostructured biointerface is fabricated via a new generation of mussel-inspired polymer coating to mimic the native ECM structures. Upon the bioinert background presence and biospecific ligands conjugation, the affinity of cancer cells to the resulting biofunctional surfaces, which integrate topographic features and biochemical cues, is greatly strengthened. Both the conjugated bioligand density, filopodia formation, and focal adhesion expression are significantly enhanced by the surficial nano-features with an optimized size-scale. Thus, this nanostructured biointerface exhibits high capture efficiency for circulating tumor cells (CTCs) with high sensitivity, high biospecificity, and high purity. Benefiting from the unique bioligands conjugation chemistry herein, the captured cancer cells can be responsively detached from the biointerfaces without damage for downstream analysis. The present biofunctional nanostructured interfaces offer a good solution to address current challenges to efficiently isolate rare CTCs from blood samples for earlier cancer diagnosis.
    MeSH term(s) Cell Adhesion ; Cell Separation ; Epithelial Cell Adhesion Molecule ; Humans ; Nanostructures ; Neoplastic Cells, Circulating ; Polymers
    Chemical Substances Epithelial Cell Adhesion Molecule ; Polymers
    Language English
    Publishing date 2021-05-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202002202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: A fast open-source Fiji-macro to quantify virus infection and transfection on single-cell level by fluorescence microscopy.

    Kerkhoff, Yannic / Wedepohl, Stefanie / Nie, Chuanxiong / Ahmadi, Vahid / Haag, Rainer / Block, Stephan

    MethodsX

    2022  Volume 9, Page(s) 101834

    Abstract: The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy ... ...

    Abstract The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy images with single-cell resolution. The macro presented here was validated by successful reconstruction of fluorescent and non-fluorescent cell mixing ratios (for fluorescence fractions ranging between 0 and 100%) and applied to quantify the efficiency of transfection and virus infection inhibition. It performed well compared with manually obtained image quantification data. Its use is not limited to the cases shown here but is applicable for most monolayered cellular assays with nuclei staining. We provide a detailed description of how the macro works and how it is applied to image data. It can be downloaded free of charge and may be used by and modified according to the needs of the user. • Rapid, simple, and reproducible segmentation of eukaryotic cells in confluent cellular assays • Open-source software for use without technical or computational expertise • Single-cell analysis allows identification and quantification of virus infected cell populations and infection inhibition.
    Language English
    Publishing date 2022-09-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2022.101834
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Scaffold Flexibility Controls Binding of Herpes Simplex Virus Type 1 with Sulfated Dendritic Polyglycerol Hydrogels Fabricated by Thiol-Maleimide Click Reaction.

    Thongrom, Boonya / Sharma, Antara / Nie, Chuanxiong / Quaas, Elisa / Raue, Marwin / Bhatia, Sumati / Haag, Rainer

    Macromolecular bioscience

    2022  Volume 22, Issue 5, Page(s) e2100507

    Abstract: Herpes Simplex Virus-1 (HSV-1) with a diameter of 155-240 nm uses electrostatic interactions to bind with the heparan sulfate present on the cell surface to initiate infection. In this work, the initial contact using polysulfate-functionalized hydrogels ... ...

    Abstract Herpes Simplex Virus-1 (HSV-1) with a diameter of 155-240 nm uses electrostatic interactions to bind with the heparan sulfate present on the cell surface to initiate infection. In this work, the initial contact using polysulfate-functionalized hydrogels is aimed to deter. The hydrogels provide a large contact surface area for viral interaction and sulfated hydrogels are good mimics for the native heparan sulfate. In this work, hydrogels of different flexibilities are synthesized, determined by rheology. Gels are prepared within an elastic modulus range of 10-1119 Pa with a mesh size of 80-15 nm, respectively. The virus binding studies carried out with the plaque assay show that the most flexible sulfated hydrogel performs the best in binding HSV viruses. These studies prove that polysulfated hydrogels are a viable option as HSV-1 antiviral compounds. Furthermore, such hydrogel networks are also physically similar to naturally occurring mucus gels and therefore may be used as mucus substitutes.
    MeSH term(s) Glycerol ; Heparitin Sulfate ; Herpesvirus 1, Human ; Hydrogels ; Maleimides ; Polymers ; Sulfates ; Sulfhydryl Compounds
    Chemical Substances Hydrogels ; Maleimides ; Polymers ; Sulfates ; Sulfhydryl Compounds ; polyglycerol (25618-55-7) ; Heparitin Sulfate (9050-30-0) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2022-02-23
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2039130-4
    ISSN 1616-5195 ; 1616-5187
    ISSN (online) 1616-5195
    ISSN 1616-5187
    DOI 10.1002/mabi.202100507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: A fast open-source Fiji-macro to quantify virus infection and transfection on single-cell level by fluorescence microscopy

    Kerkhoff, Yannic / Wedepohl, Stefanie / Nie, Chuanxiong / Ahmadi, Vahid / Haag, Rainer / Block, Stephan

    MethodsX. 2022, v. 9

    2022  

    Abstract: The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy ... ...

    Abstract The ability to automatically analyze large quantities of image data is a valuable tool for many biochemical assays, as it rapidly provides reliable data. Here, we describe a fast and robust Fiji macro for the analysis of cellular fluorescence microscopy images with single-cell resolution. The macro presented here was validated by successful reconstruction of fluorescent and non-fluorescent cell mixing ratios (for fluorescence fractions ranging between 0 and 100%) and applied to quantify the efficiency of transfection and virus infection inhibition. It performed well compared with manually obtained image quantification data. Its use is not limited to the cases shown here but is applicable for most monolayered cellular assays with nuclei staining. We provide a detailed description of how the macro works and how it is applied to image data. It can be downloaded free of charge and may be used by and modified according to the needs of the user. • Rapid, simple, and reproducible segmentation of eukaryotic cells in confluent cellular assays • Open-source software for use without technical or computational expertise • Single-cell analysis allows identification and quantification of virus infected cell populations and infection inhibition
    Keywords computer software ; fluorescence ; fluorescence microscopy ; transfection ; viruses ; Fiji
    Language English
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2022.101834
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures.

    Pouyan, Paria / Nie, Chuanxiong / Bhatia, Sumati / Wedepohl, Stefanie / Achazi, Katharina / Osterrieder, Nikolaus / Haag, Rainer

    Biomacromolecules

    2021  Volume 22, Issue 4, Page(s) 1545–1554

    Abstract: Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors ... ...

    Abstract Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demonstrate the inhibitory effect of a polymer scaffold on the HSV-1 infection by using highly sulfated polyglycerols with different architectures (linear, dendronized, and hyperbranched). IC
    MeSH term(s) Antiviral Agents/pharmacology ; Glycerol ; Herpesvirus 1, Human ; Polymers ; Sulfates
    Chemical Substances Antiviral Agents ; Polymers ; Sulfates ; polyglycerol (25618-55-7) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2021-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1526-4602
    ISSN (online) 1526-4602
    DOI 10.1021/acs.biomac.0c01789
    Database MEDical Literature Analysis and Retrieval System OnLINE

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