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  1. Article ; Online: Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease

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

    Life, Vol 13, Iss 680, p

    In-Silico Analysis

    2023  Volume 680

    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.
    Keywords inflammatory bowel disease ; in-silico ; transcriptomics ; differentially expressed gene analysis ; infliximab treatment response ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Novel Markers in Pediatric Acute Lymphoid Leukemia

    Laila Alsuwaidi / Mahmood Hachim / Abiola Senok

    Frontiers in Cell and Developmental Biology, Vol

    The Role of ADAM6 in B Cell Leukemia

    2021  Volume 9

    Abstract: BackgroundThe extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out in silico analysis ...

    Abstract BackgroundThe extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out in silico analysis of publicly available ALL datasets to identify genetic biomarkers for childhood BCP-ALL, which could be used either individually or in combination as markers for early detection, risk stratification, and prognosis.MethodsTo explore novel genes that show promising clinical and molecular signatures, we examined the cBioPortal online tool for publicly available datasets on lymphoid cancers. Three studies on lymphoblastic and lymphoid leukemia with 1706 patients and 2144 samples of which were identified. Only B-Lymphoblastic Leukemia/Lymphoma samples (n = 1978) were selected for further analysis. Chromosomal changes were assessed to determine novel genomic loci to analyze clinical and molecular profiles for the leukemia of lymphoid origin using cBioPortal tool.ResultsADAM6 gene homozygous deletions (HOM:DEL) were present in 59.60% of the profiled patients and were associated with poor ten years of overall patients’ survival. Moreover, patients with ADAM6 HOM:DEL showed a distinguished clinical and molecular profile with higher Central Nervous System (CNS) sites of relapse. In addition, ADAM6 HOM:DEL was significantly associated with unique microRNAs gene expression patterns.ConclusionADAM6 has the potential to be a novel biomarker for the development and progress of BCP- ALL.
    Keywords ADAM6 ; acute lymphoid leukemia ; bioinformactics analysis ; biomarkers ; pediatric leukemia ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Simulated Microgravity Influences Immunity-Related Biomarkers in Lung Cancer

    Hend Baghoum / Hend Alahmed / Mahmood Hachim / Abiola Senok / Nour Jalaleddine / Saba Al Heialy

    International Journal of Molecular Sciences, Vol 24, Iss 1, p

    2022  Volume 155

    Abstract: Microgravity is a novel strategy that may serve as a complementary tool to develop future cancer therapies. In lung cancer, the influence of microgravity on cellular processes and the migratory capacity of cells is well addressed. However, its effect on ... ...

    Abstract Microgravity is a novel strategy that may serve as a complementary tool to develop future cancer therapies. In lung cancer, the influence of microgravity on cellular processes and the migratory capacity of cells is well addressed. However, its effect on the mechanisms that drive lung cancer progression remains in their infancy. In this study, 13 differentially expressed genes were shown to be associated with the prognosis of lung cancer under simulated microgravity (SMG). Using gene set enrichment analysis, these genes are enriched in humoral immunity pathways. In lieu, alveolar basal-epithelial (A549) cells were exposed to SMG via a 2D clinostat system in vitro. In addition to morphology change and decrease in proliferation rate, SMG reverted the epithelial-to-mesenchymal transition (EMT) phenotype of A549, a key mechanism in cancer progression. This was evidenced by increased epithelial E-cadherin expression and decreased mesenchymal N-cadherin expression, hence exhibiting a less metastatic state. Interestingly, we observed increased expression of FCGBP , BPIFB , F5 , CST1 , and CFB and their correlation to EMT under SMG, rendering them potential tumor suppressor biomarkers. Together, these findings reveal new opportunities to establish novel therapeutic strategies for lung cancer treatment.
    Keywords simulated microgravity ; EMT ; lung cancer ; metastasis ; tumor suppressor ; biomarkers ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection

    Mellissa Gaudet / Eva Kaufmann / Nour Jalaleddine / Andrea Mogas / Mahmood Hachim / Abiola Senok / Maziar Divangahi / Qutayba Hamid / Saba Al Heialy

    International Journal of Molecular Sciences, Vol 24, Iss 6729, p

    2023  Volume 6729

    Abstract: Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly ... ...

    Abstract Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly elucidated. This study aims to better understand the effect of obesity on the course of SARS-CoV-2 infection and identify candidate molecular pathways involved in the progression of the disease, using an in vitro live infection model and RNA sequencing. Results from this study revealed the enhancement of viral load and replication in bronchial epithelial cells (NHBE) from obese subjects at 24 h of infection (MOI = 0.5) as compared to non-obese subjects. Transcriptomic profiling via RNA-Seq highlighted the enrichment of lipid metabolism-related pathways along with LPIN2 , an inflammasome regulator, as a unique differentially expressed gene (DEG) in infected bronchial epithelial cells from obese subjects. Such findings correlated with altered cytokine and angiotensin-converting enzyme-2 (ACE2) expression during infection of bronchial cells. These findings provide a novel insight on the molecular interplay between obesity and SARS-CoV-2 infection. In conclusion, this study demonstrates the increased SARS-CoV-2 infection of bronchial epithelial cells from obese subjects and highlights the impaired immunity which may explain the increased severity among obese COVID-19 patients.
    Keywords SARS-CoV-2 ; infection ; obesity ; immune response ; ACE2 ; transcriptome profiling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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