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  • 1
    Online Resource
    Online Resource
    Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers
    Hindawi Limited ; 2020
    In:  Disease Markers Vol. 2020 ( 2020-08-27), p. 1-16
    Details
    In: Disease Markers, Hindawi Limited, Vol. 2020 ( 2020-08-27), p. 1-16
    Abstract: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide in part due to the concomitant obesity pandemic and insulin resistance (IR). It is increasingly becoming evident that NAFLD is a disease affecting numerous extrahepatic vital organs and regulatory pathways. The molecular mechanisms underlying the nonalcoholic steatosis formation are poorly understood, and little information is available on the pathways that are responsible for the progressive hepatocellular damage that follows lipid accumulation. Recently, much research has focused on the identification of the epigenetic modifications that contribute to NAFLD pathogenesis. Noncoding RNAs (ncRNAs) are one of such epigenetic factors that could be implicated in the NAFLD development and progression. In this review, we summarize the current knowledge of the genetic and epigenetic factors potentially underlying the disease. Particular emphasis will be put on the contribution of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) to the pathophysiology of NAFLD as well as their potential use as therapeutic targets or as markers for the prediction and the progression of the disease.
    Type of Medium: Online Resource
    ISSN: 0278-0240 , 1875-8630
    URL: Article
    DOI: 10.1155/2020/8822859
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2033253-1
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  • 2
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    Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 14 ( 2023-07-18), p. 11606-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 14 ( 2023-07-18), p. 11606-
    Abstract: Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241411606
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
    Springer Science and Business Media LLC ; 2021
    In:  Journal of Translational Medicine Vol. 19, No. 1 ( 2021-06-02)
    Details
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-06-02)
    Abstract: The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    URL: Article
    DOI: 10.1186/s12967-021-02885-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2118570-0
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  • 4
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    Comprehensive analysis of circulating miRNA expression profiles in insulin resistance and type 2 diabetes in Qatari population
    Informa UK Limited ; 2022
    In:  All Life Vol. 15, No. 1 ( 2022-12-31), p. 191-202
    Details
    In: All Life, Informa UK Limited, Vol. 15, No. 1 ( 2022-12-31), p. 191-202
    Type of Medium: Online Resource
    ISSN: 2689-5293 , 2689-5307
    URL: Article
    DOI: 10.1080/26895293.2022.2033853
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 3068631-3
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  • 5
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    Simple risk score to screen for prediabetes: A cross‐sectional study from the Qatar Biobank cohort
    Wiley ; 2021
    In:  Journal of Diabetes Investigation Vol. 12, No. 6 ( 2021-06), p. 988-997
    Details
    In: Journal of Diabetes Investigation, Wiley, Vol. 12, No. 6 ( 2021-06), p. 988-997
    Abstract: The progression from prediabetes to type 2 diabetes is preventable by lifestyle intervention and/or pharmacotherapy in a large fraction of individuals with prediabetes. Our objective was to develop a risk score to screen for prediabetes in the Middle East, where diabetes prevalence is one of the highest in the world. Materials and Methods In this cross‐sectional, case–control study, we used data of 4,895 controls and 2,373 prediabetic adults obtained from the Qatar Biobank cohort. Significant risk factors were identified by logistic regression and other machine learning methods. The receiver operating characteristic was used to calculate the area under curve, cut‐off point, sensitivity, specificity, positive and negative predictive values. The prediabetes risk score was developed from data of Qatari citizens, as well as long‐term (≥15 years) residents. Results The significant risk factors for the Prediabetes Risk Score in Qatar were age, sex, body mass index, waist circumference and blood pressure. The risk score ranges from 0 to 45. The area under the curve of the score was 80% (95% confidence interval 78–83%), and the cut‐off point of 16 yielded sensitivity and specificity of 86.2% (95% confidence interval 82.7–89.2%) and 57.9% (95% confidence interval 65.5–71.4%), respectively. Prediabetes Risk Score in Qatar performed equally in Qatari nationals and long‐term residents. Conclusions Prediabetes Risk Score in Qatar is the first prediabetes screening score developed in a Middle Eastern population. It only uses risk factors measured non‐invasively, is simple, cost‐effective, and can be easily understood by the general public and health providers. Prediabetes Risk Score in Qatar is an important tool for early detection of prediabetes, and can help tremendously in curbing the diabetes epidemic in the region.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    URL: Article
    DOI: 10.1111/jdi.v12.6
    DOI: 10.1111/jdi.13445
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2542077-X
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  • 6
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    Exendin-4 alleviates steatosis in an in vitro cell model by lowering FABP1 and FOXA1 expression via the Wnt/-catenin signaling pathway
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-02-09)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-02-09)
    Abstract: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Agonists of the glucagon-like peptide-1 receptor (GLP-1R), currently approved to treat type 2 diabetes, hold promise to improve steatosis and even steatohepatitis. However, due to their pleiotropic effects, the mechanisms underlying their protective effect on NAFLD remain elusive. We aimed to investigate these mechanisms using an in vitro model of steatosis treated with the GLP-1R agonist Exendin-4 (Ex-4). We established steatotic HepG2 cells by incubating the cells with 400 µM oleic acid (OA) overnight. Further treatment with 200 nM Ex-4 for 3 h significantly reduced the OA-induced lipid accumulation (p  〈  0.05). Concomitantly, Ex-4 substantially reduced the expression levels of Fatty Acid-Binding Protein 1 (FABP1) and its primary activator, Forkhead box protein A1 (FOXA1). Interestingly, the silencing of β-catenin with siRNA abolished the effect of Ex-4 on these genes, suggesting dependency on the Wnt/β-catenin pathway. Additionally, after β-catenin silencing, OA treatment significantly increased the expression of nuclear transcription factors SREBP-1 and TCF4, whereas Ex-4 significantly decreased this upregulation. Our findings suggest that direct activation of GLP-1R by Ex-4 reduces OA-induced steatosis in HepG2 cells by reducing fatty acid uptake and transport via FABP1 downregulation.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-06143-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 7
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    OutPyR: Bayesian inference for RNA-Seq outlier detection
    Elsevier BV ; 2020
    In:  Journal of Computational Science Vol. 47 ( 2020-11), p. 101245-
    Details
    In: Journal of Computational Science, Elsevier BV, Vol. 47 ( 2020-11), p. 101245-
    Type of Medium: Online Resource
    ISSN: 1877-7503
    URL: Article
    DOI: 10.1016/j.jocs.2020.101245
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2557360-3
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  • 8
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    Identification of potential transcription factors that enhance human iPSC generation
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-12-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-12-15)
    Abstract: Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) ( GBX2, NANOGP8, SP8, PEG3, and ZIC1 ) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4 . Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-78932-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 9
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    DataSheet1.docx
    Frontiers Media SA ; 2024
    In:  Frontiers in Genetics Vol. 15 ( 2024-3-20)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 15 ( 2024-3-20)
    Abstract: Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk. Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents). Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD ( DTX4 , ARMC6 , and B3GNT3 ). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders ( PHF21A , WASF1 , TCF20 , DEAF1 , MED13 , CREBBP , KDM6B, SMURF1 , ADNP , CACNA1G , MYT1L , KIF13B , GRIA2 , CHM , and KCNK9 ). Additionally, we defined eight novel recessive variants ( RYR2 , DNAH3 , TSPYL2 , UPF3B KDM5C , LYST , and WNK3 ), four of which were X-linked. Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    URL: Article
    DOI: 10.3389/fgene.2024.1363849
    DOI: 10.3389/fgene.2024.1363849.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2606823-0
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  • 10
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    FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis
    Elsevier BV ; 2023
    In:  Gene Vol. 887 ( 2023-12), p. 147791-
    Details
    In: Gene, Elsevier BV, Vol. 887 ( 2023-12), p. 147791-
    Type of Medium: Online Resource
    ISSN: 0378-1119
    URL: Article
    DOI: 10.1016/j.gene.2023.147791
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1491012-3
    SSG: 12
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