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  1. Article ; Online: RBM25 binds to and regulates alternative splicing levels of Slc38a9, Csf1, and Coro6 to affect immune and inflammatory processes in H9c2 cells

    Xin Tian / Guangli Zhou / Hao Li / Xueting Zhang / Lingmin Zhao / Keyi Zhang / Luqiao Wang / Mingwei Liu / Chen Liu / Ping Yang

    PeerJ, Vol 11, p e

    2023  Volume 16312

    Abstract: Background Alternative splicing (AS) is a biological process that allows genes to be translated into diverse proteins. However, aberrant AS can predispose cells to aberrations in biological mechanisms. RNA binding proteins (RBPs), closely affiliated with ...

    Abstract Background Alternative splicing (AS) is a biological process that allows genes to be translated into diverse proteins. However, aberrant AS can predispose cells to aberrations in biological mechanisms. RNA binding proteins (RBPs), closely affiliated with AS, have gained increased attention in recent years. Among these RBPs, RBM25 has been reported to participate in the cardiac pathological mechanism through regulating AS; however, the involvement of RBM25 as a splicing factor in heart failure remains unclarified. Methods RBM25 was overexpressed in H9c2 cells to explore the target genes bound and regulated by RBM25 during heart failure. RNA sequencing (RNA-seq) was used to scrutinize the comprehensive transcriptional level before identifying AS events influenced by RBM25. Further, improved RNA immunoprecipitation sequencing (iRIP-seq) was employed to pinpoint RBM25-binding sites, and RT-qPCR was used to validate specific genes modulated by RBM25. Results RBM25 was found to upregulate the expression of genes pertinent to the inflammatory response and viral processes, as well as to mediate the AS of genes associated with cellular apoptosis and inflammation. Overlap analysis between RNA-seq and iRIP-seq suggested that RBM25 bound to and manipulated the AS of genes associated with inflammation in H9c2 cells. Moreover, qRT-PCR confirmed Slc38a9, Csf1, and Coro6 as the binding and AS regulatory targets of RBM25. Conclusion Our research implies that RBM25 plays a contributory role in cardiac inflammatory responses via its ability to bind to and regulate the AS of related genes. This study offers preliminary evidence of the influence of RBM25 on inflammation in H9c2 cells.
    Keywords RBM25 ; Alternative splicing ; RNA-seq ; Improved RNA immunoprecipitation sequencing ; Inflammation ; H9c2 cell ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Single‐cell profiling‐guided combination therapy of c‐Fos and histone deacetylase inhibitors in diffuse large B‐cell lymphoma

    Luqiao Wang / Zijuan Wu / Yi Xia / Xueying Lu / Ji Li / Lei Fan / Chun Qiao / Hairong Qiu / Danling Gu / Wei Xu / Jianyong Li / Hui Jin

    Clinical and Translational Medicine, Vol 12, Iss 5, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. ... ...

    Abstract Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy. Methods The antitumour effects of the drug were evaluated by Cell Counting Kit‐8 (CCK‐8) assay and apoptosis analysis. Single‐cell RNA sequencing (scRNA‐Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole‐exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT–PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models. Results LAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA‐Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c‐Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c‐Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo. Conclusion Altogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi‐based combination therapy strategy.
    Keywords combination treatment ; diffuse large B‐cell lymphoma ; histone deacetylase inhibitor ; single‐cell RNA sequencing ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Reply to Comment on Shen H, et al. “Co-signaling receptors regulate T-cell plasticity and immune tolerance”. Frontiers in Bioscience-Landmark. 2019; 24

    Haitao Shen / Na Wu / Gayani Nanayakkara / Hangfei Fu / Qian Yang / William Y. Yang / Angus Li / Yu Sun / Charles Drummer IV / Candice Johnson / Ying Shao / Luqiao Wang / Keman Xu / Wenhui Hu / Marion Chan / Vincent Tam / Eric T. Choi / Hong Wang / Xiaofeng Yang

    Frontiers in Bioscience-Landmark, Vol 26, Iss 10, Pp 678-

    96–132

    2021  Volume 679

    Keywords Biochemistry ; QD415-436 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher IMR Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Xinmailong Modulates Platelet Function and Inhibits Thrombus Formation via the Platelet αIIbβ3-Mediated Signaling Pathway

    Huawei Wang / Yujia Ye / Wen Wan / Luqiao Wang / Ruijie Li / Longjun Li / Lihong Yang / Lai Yang / Yajuan Gu / Ling Dong / Zhaohui Meng

    Frontiers in Pharmacology, Vol

    2019  Volume 10

    Abstract: Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic ... ...

    Abstract Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects.Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model.Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen–epinephrine-induced acute pulmonary thrombosis mouse model.Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.
    Keywords Xinmailong ; platelet ; thrombosis ; α II bβ3 ; traditional medicine ; Therapeutics. Pharmacology ; RM1-950
    Subject code 070
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Plasma exosomes induced by remote ischaemic preconditioning attenuate myocardial ischaemia/reperfusion injury by transferring miR-24.

    Minghua, Wen / Zhijian, Gong / Chahua, Huang / Qiang, Liang / Minxuan, Xu / Luqiao, Wang / Weifang, Zhang / Peng, Lu / Biming, Zhan / Lingling, Yu / Zhenzhen, Wang / Jianqing, Xu / Huihui, Bao / Xiaozhong, Wang / Xiaoshu, Cheng

    Cell death & disease

    2018  Volume 9, Issue 3, Page(s) 320

    Abstract: Remote ischaemic preconditioning (RIPC) is well known to protect the myocardium against ischaemia/reperfusion injury (IRI). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. Various studies have ... ...

    Abstract Remote ischaemic preconditioning (RIPC) is well known to protect the myocardium against ischaemia/reperfusion injury (IRI). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. Various studies have confirmed that circulating exosomes mediate RIPC. However, the underlying mechanisms for RIPC-induced exosome-mediated cardioprotection remain elusive. In our study, we found that the expression level of miR-24 was higher in exosomes derived from the plasma of rats subjected to RIPC than in exosomes derived from the plasma of control rats in vivo. The rat plasma exosomes could be taken up by H9c2 cells. In addition, miR-24 was present in RIPC-induced exosomes and played a role in reducing oxidative stress-mediated injury and decreasing apoptosis by downregulating Bim expression in H
    MeSH term(s) Animals ; Apoptosis ; Disease Models, Animal ; Exosomes/metabolism ; Hydrogen Peroxide/toxicity ; Ischemic Preconditioning, Myocardial ; Male ; Mice ; MicroRNAs/therapeutic use ; Models, Biological ; Myocardial Reperfusion Injury/blood ; Myocardial Reperfusion Injury/genetics ; Myocardial Reperfusion Injury/therapy ; Myocytes, Cardiac/metabolism ; Rats, Sprague-Dawley
    Chemical Substances MIRN24 microRNA, rat ; MicroRNAs ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2018-02-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-018-0274-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression

    Luqiao Wang / Hangfei Fu / Gayani Nanayakkara / Yafeng Li / Ying Shao / Candice Johnson / Jiali Cheng / William Y. Yang / Fan Yang / Muriel Lavallee / Yanjie Xu / Xiaoshu Cheng / Hang Xi / Jonathan Yi / Jun Yu / Eric T. Choi / Hong Wang / Xiaofeng Yang

    Journal of Hematology & Oncology, Vol 9, Iss 1, Pp 1-

    a comprehensive database mining study

    2016  Volume 18

    Abstract: Abstract Background Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only ...

    Abstract Abstract Background Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. Methods We conducted meticulous data analysis methods on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies. Results We made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation. Conclusions Our identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers.
    Keywords Caspase-1 ; Trafficking ; Nuclear gene regulation ; Inflammation propagation ; Exosome ; Diseases of the blood and blood-forming organs ; RC633-647.5 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 570
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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