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Ghada Nour Eldeen

Publications and source records attributed to Ghada Nour Eldeen.

2 recordsLinked to original sources
PubMed2026

PIP3 antagonist as a molecular regulator in MSC-derived cardiomyocytes: Potential in vitro therapeutic implications for conotruncal heart defects.

Conotruncal heart defects (CTDs) account for approximately one-third of all congenital heart defects. Elevated levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) may contribute to CTD pathogenesis. PIP3 plays a pivotal role in mechanotransduction-based biological processes and remodeling of cardiac cytoskeletal proteins. Here, we aimed to evaluate the efficacy of the 322PESB derivative compound as a molecular regulator that antagonizes PIP3 binding pleckstrin homology (PH) domain of the Akt protein using mesenchymal stem cell-derived cardiomyocyte. Human adipose-derived MSCs (Ad-MSCs) were isolated. Immunophenotypic features of the hAd-MSCs were characterized according to minimal criteria of the international society for cellular therapy (ISCT) including immunophenotyping and trilineage differentiation potential. Subsequently, the differentiated hAd-MSCs were cultured in cardiomyogenesis-inducing medium. Successfully differentiated cardiomyocytes were assessed by measuring the expression levels of cardiomyocyte-specific genes using RT-qPCR. PIP3-primed cardiomyocytes were treated with 10 and 30 μmol/L of a 322PESB derivative molecule. The results showed a typical MSCs with high expression levels of CD73 (77.55%), CD90 (87.59%) and CD105 (91.88%) and that was accompanied by low expression levels of CD34 (0.59%) and CD45 (1.78%). After 21 days of MSC culture, cardiomyocyte-like cells with prominent striations were observed. Subsequent confirmation by RT-qPCR quantification of ADRB1 and MLC2a expression levels showed an average increase of 2.9-fold and 2.1-fold, respectively, in induced cardiomyocytes. Compared with the untreated control, PIP3 ELISA assay showed a significant increase in PIP3 levels in PIP3(10 nmol/L)-primed cardiomyocytes treated with 10 and 30 μmol/L of the 322PESB molecule derivative by 485.804 and 3564.164 ng/mL, respectively. In this study, we conducted the first promising molecular regulator with potential therapeutic implications for CTD patients. Further functional animal model and clinical phase studies are recommended.

Cardiomyocyte↗
PubMed2026

Targeted Epigenetic Silencing of Jumonji Domain-Containing Protein 3 Alleviates Nuclear Factor-Kappa B-Mediated Inflammation in Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an inherited autoinflammatory condition caused by variants in the MEFV gene encoding pyrin, the essential component of the NLRP3/NF-κB complex of inflammasomes. Deregulation of nuclear factor-kappa B (NF-κB), a key proinflammatory mediator, leads to chronic inflammation in autoinflammatory/autoimmune diseases. Epigenetic modulation offers a new approach to regulate inflammasome activity, with Jumonji domain-containing protein 3 (JMJD3) being a promising target for managing inflammatory illnesses. GSK-J4 is a selective inhibitor of JMJD3, restricting pro-inflammatory cytokines and inflammation. AIM: Our research aimed to elucidate the role of JMJD3 and the NF-κB-JMJD3 signaling pathways in regulating inflammation in an in vitro model, and to investigate GSK-J4's effect in inhibiting inflammasome activation in primed peripheral blood mononuclear cells (PBMCs) isolated from FMF cases. METHODS: PBMCs were cultured and primed with LPS, and then treated with GSK-J4. JMJD3 knockdown was achieved using siRNA interference. Cellular inflammatory dynamics were assessed by Western blotting (WB) and ELISA. The qRT-PCR was used for gene expression quantification. Untreated cells served as a negative control. RESULTS: Our results showed significantly downregulated gene expression of NF-κB, NLRP3, and inflammatory cytokines in GSK-J4-treated cells compared to untreated cells, as confirmed by ELISA. WB reported a reduction of NF-κB in induced cells following GSK-J4 treatment. Knocking down JMJD3 also showed decreased levels of JMJD3, NF-κB, and inflammatory cytokines, indicating its proinflammatory role. CONCLUSION: The study showed that selective inhibition or silencing of JMJD3 significantly suppressed the inflammasome in FMF cases, suggesting its role as a therapeutic target for alleviating inflammation in various autoinflammatory diseases.

Humans↗