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  1. Article: Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis.

    Kaddoura, Rachid / Ghelani, Hardik / Alqutami, Fatma / Altaher, Hala / Hachim, Mahmood / Jan, Reem Kais

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 3

    Abstract: Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, ... ...

    Abstract Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response.
    Methods: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes.
    Results: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group.
    Conclusions: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.
    Language English
    Publishing date 2023-03-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13030680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CD154-CD40 interactions in the control of murine B cell hematopoiesis.

    Carlring, Jennifer / Altaher, Hala M / Clark, Susan / Chen, Xi / Latimer, Sarah L / Jenner, Tracey / Buckle, Anne-Marie / Heath, Andrew W

    Journal of leukocyte biology

    2011  Volume 89, Issue 5, Page(s) 697–706

    Abstract: Interactions between CD40 and CD154 play a very important role in control of immune responses, including the delivery of T cell help to B cells and other APCs. Thus far, there has been no role postulated for CD40-CD154 interactions in hematopoiesis. We ... ...

    Abstract Interactions between CD40 and CD154 play a very important role in control of immune responses, including the delivery of T cell help to B cells and other APCs. Thus far, there has been no role postulated for CD40-CD154 interactions in hematopoiesis. We show here that CD40 is expressed on murine pro-B cells and that its ligation enhances pro-B cell proliferation in vitro and in vivo. In addition, CD154 mRNA is present in the BM. Moreover, we show that a deficiency in CD154 expression has effects on B cell hematopoiesis. Aged, CD154-deficient mice have significantly lower levels of B hematopoietic subsets downstream of pro-B cells in the BM. In addition, B lineage cells reconstitute more slowly following BMT into CD154-deficient recipients. We hypothesize that CD154 is expressed by radio-resistant cells in the BM and plays a role in fine-tuning B cell hematopoiesis.
    MeSH term(s) Animals ; B-Lymphocytes/physiology ; Blotting, Western ; Bone Marrow/metabolism ; Bone Marrow Transplantation ; CD40 Antigens/metabolism ; CD40 Ligand/metabolism ; Cell Proliferation ; Coculture Techniques ; Female ; Fibroblasts/metabolism ; Hematopoiesis ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Precursor Cells, B-Lymphoid/metabolism ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances CD40 Antigens ; RNA, Messenger ; CD40 Ligand (147205-72-9)
    Language English
    Publishing date 2011-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.0310179
    Database MEDical Literature Analysis and Retrieval System OnLINE

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