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  1. Article ; Online: An engineered TNFR1-selective human lymphotoxin-alpha mutant delivered by an oncolytic adenovirus for tumor immunotherapy.

    Cheng, Yan / Liu, Yu / Xu, Dongge / Zhang, Dan / Yang, Yang / Miao, Yuqing / He, Susu / Xu, Qing / Li, Erguang

    Biochimica et biophysica acta. Molecular basis of disease

    2024  Volume 1870, Issue 5, Page(s) 167122

    Abstract: Lymphotoxin α (LTα) is a soluble factor produced by activated lymphocytes which is cytotoxic to tumor cells. Although a promising candidate in cancer therapy, the application of recombinant LTα has been limited by its instability and toxicity by systemic ...

    Abstract Lymphotoxin α (LTα) is a soluble factor produced by activated lymphocytes which is cytotoxic to tumor cells. Although a promising candidate in cancer therapy, the application of recombinant LTα has been limited by its instability and toxicity by systemic administration. Secreted LTα interacts with several distinct receptors for its biological activities. Here, we report a TNFR1-selective human LTα mutant (LTα Q107E) with potent antitumor activity. Recombinant LTα Q107E with N-terminal 23 and 27 aa deletion (named LTα Q1 and Q2, respectively) showed selectivity to TNFR1 in both binding and NF-κB pathway activation assays. To test the therapeutic potential, we constructed an oncolytic adenovirus (oAd) harboring LTα Q107E Q2 mutant (named oAdQ2) and assessed the antitumor effect in mouse xenograft models. Intratumoral delivery of oAdQ2 inhibited tumor growth. In addition, oAdQ2 treatment enhanced T cell and IFNγ-positive CD8 T lymphocyte infiltration in a human PBMC reconstituted-SCID mouse xenograft model. This study provides evidence that reengineering of bioactive cytokines with tissue or cell specific properties may potentiate their therapeutic potential of cytokines with multiple receptors.
    Language English
    Publishing date 2024-03-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbadis.2024.167122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: LINE-1 repression in Epstein-Barr virus-associated gastric cancer through viral-host genome interaction.

    Zhang, Mengyu / Sun, Weikang / You, Xiaoxin / Xu, Dongge / Wang, Lingling / Yang, Jingping / Li, Erguang / He, Susu

    Nucleic acids research

    2023  Volume 51, Issue 10, Page(s) 4867–4880

    Abstract: Long INterspersed Element 1 (LINE-1 or L1) acts as a major remodeling force in genome regulation and evolution. Accumulating evidence shows that virus infection impacts L1 expression, potentially impacting host antiviral response and diseases. The ... ...

    Abstract Long INterspersed Element 1 (LINE-1 or L1) acts as a major remodeling force in genome regulation and evolution. Accumulating evidence shows that virus infection impacts L1 expression, potentially impacting host antiviral response and diseases. The underlying regulation mechanism is unclear. Epstein-Barr virus (EBV), a double-stranded DNA virus linked to B-cell and epithelial malignancies, is known to have viral-host genome interaction, resulting in transcriptional rewiring in EBV-associated gastric cancer (EBVaGC). By analyzing publicly available datasets from the Gene Expression Omnibus (GEO), we found that EBVaGC has L1 transcriptional repression compared with EBV-negative gastric cancer (EBVnGC). More specifically, retrotransposition-associated young and full-length L1s (FL-L1s) were among the most repressed L1s. Epigenetic alterations, especially increased H3K9me3, were observed on FL-L1s. H3K9me3 deposition was potentially attributed to increased TASOR expression, a key component of the human silencing hub (HUSH) complex for H3K9 trimethylation. The 4C- and HiC-seq data indicated that the viral DNA interacted in the proximity of the TASOR enhancer, strengthening the loop formation between the TASOR enhancer and its promoter. These results indicated that EBV infection is associated with increased H3K9me3 deposition, leading to L1 repression. This study uncovers a regulation mechanism of L1 expression by chromatin topology remodeling associated with viral-host genome interaction in EBVaGC.
    MeSH term(s) Humans ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/genetics ; Herpesvirus 4, Human/genetics ; Nuclear Proteins ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Long Interspersed Nucleotide Elements ; Host-Pathogen Interactions
    Chemical Substances Nuclear Proteins ; TASOR protein, human
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment.

    Li, Jingjing / Xu, Dongge / Wang, Lingling / Zhang, Mengyu / Zhang, Guohai / Li, Erguang / He, Susu

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 20

    Abstract: Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants ... ...

    Abstract Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of
    MeSH term(s) Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/metabolism ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Binding Sites ; COVID-19/virology ; Glycyrrhizic Acid/chemistry ; Glycyrrhizic Acid/metabolism ; Glycyrrhizic Acid/pharmacology ; Glycyrrhizic Acid/therapeutic use ; Humans ; Molecular Docking Simulation ; Protein Binding ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization/drug effects ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Glycyrrhizic Acid (6FO62043WK) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-10-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26206090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of Tonsil Microbiota and Their Effect on Adenovirus Reactivation in Tonsillectomy Samples.

    Wang, Lingling / Xu, Dongge / Huang, Qun / Yang, Guang / Zhang, Mengyu / Bi, Jingai / Shan, Jinjun / Li, Erguang / He, Susu

    Microbiology spectrum

    2021  Volume 9, Issue 2, Page(s) e0124621

    Abstract: The adenoviral DNA is prevalent in adenotonsillectomy specimens from pediatric patients, though the virus seems to be in latent state. The tonsils are at the forefront of airway entry point and are the first line of defense against airway viral and ... ...

    Abstract The adenoviral DNA is prevalent in adenotonsillectomy specimens from pediatric patients, though the virus seems to be in latent state. The tonsils are at the forefront of airway entry point and are the first line of defense against airway viral and bacterial infections. We hypothesized that tonsil microbiota plays a role in human adenovirus (HAdV) latency and reactivation. In this study, we surveyed the presence of HAdV in tonsillectomy samples from 81 patients and found that HAdV DNA was in 85.2% of the tonsil samples. We then determined the microbiota of the samples. Taxonomic profiling showed that
    MeSH term(s) Adenovirus Infections, Human/virology ; Adenoviruses, Human/genetics ; Adenoviruses, Human/isolation & purification ; Adenoviruses, Human/physiology ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; Child ; Child, Preschool ; DNA, Bacterial/genetics ; Fatty Acids, Volatile/metabolism ; Female ; Humans ; Infant ; Male ; Microbiota ; Palatine Tonsil/microbiology ; Palatine Tonsil/surgery ; Palatine Tonsil/virology ; RNA, Ribosomal, 16S/genetics ; Tonsillectomy ; Virus Activation ; Virus Latency ; Virus Replication
    Chemical Substances DNA, Bacterial ; Fatty Acids, Volatile ; RNA, Ribosomal, 16S
    Language English
    Publishing date 2021-10-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/Spectrum.01246-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A self-feedback network based on liquid chromatography-quadrupole-time of flight mass spectrometry for system identification of β-carboline alkaloids in Picrasma quassioides.

    Shi, Yuanyuan / Wang, Ruoqi / Zhu, Xiaoyu / Xu, Dongge / Liu, Wenyuan / Feng, Feng

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 13841

    Abstract: Profiling chemical components in herbs by mass spectrometry is a challenging work because of the lack of standard compounds, especially for position isomers. This paper provides a strategy based on a self-feedback network of mass spectra (MS) data to ... ...

    Abstract Profiling chemical components in herbs by mass spectrometry is a challenging work because of the lack of standard compounds, especially for position isomers. This paper provides a strategy based on a self-feedback network of mass spectra (MS) data to identify chemical constituents in herbs by liquid chromatography-quadrupole-time of flight mass spectrometry without compound standards. Components sharing same skeleton were screened and all ions were classified into a database. All candidates were connected by the selected bridging ions to establish a primary MS network. Benefited from such a network, it is feasible to characterize sequentially the structures of all diagnostic ions and candidates once single component has been de novo identified. Taking Picrasma quassioides as an example, the primary network of β-carbolines was established with 65 ions (selected from 76 β-carbolines), each of which appeared at least in four compounds. Once an alkaloid has been identified, its logical ions could feedback into primary network to build pathways with other unknown compounds. Moreover, the position of the substituent groups could be deduced through the secondary metabolic pathways of alkaloids (plant secondary metabolism). The network therefore can be utilized for identification of unknown compounds and even their position isomers.
    MeSH term(s) Alkaloids/analysis ; Alkaloids/isolation & purification ; Carbolines/analysis ; Carbolines/isolation & purification ; Chromatography, Liquid/methods ; Molecular Structure ; Picrasma/chemistry ; Plant Extracts/analysis ; Tandem Mass Spectrometry/methods
    Chemical Substances Alkaloids ; Carbolines ; Plant Extracts
    Language English
    Publishing date 2017-10-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-13106-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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