1.Unveiling the role of microRNAs, the PI3K/ AKT pathway, and their associations in various types of leukemia: a comprehensive review
Amir Modarresi CHAHARDEHI ; Esfandiar MALI ; Arya AFROOGHE ; Amirmasoud ASADI ; Amirreza KHALAJI ; Hamed Soleimani SAMARKHAZAN ; Hananeh Esmaeil BEYGI ; Amirhossein MOHAGHEGHI ; Maryam KHANBABAEI ; Heliya HAGHANI ; Reza AREFNEZHAD ; Fatemeh REZAEI‑TAZANGI
Blood Research 2025;60():56-
The phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway and microRNA (miRNA) regulation have been implicated in the initiation and progression of acute leukemia. Despite significant progress in the understanding of leukemogenic mechanisms, current therapies remain limited by relapse, drug resistance, and poor long-term survival, underscoring the need for novel targeted strategies. This review provides the current evidence regarding the molecular interplay between PI3K/AKT/mTOR signaling and miRNA dysregulation in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). We highlight key oncogenic and tumorsuppressive miRNAs, discuss their regulatory impact on critical genes (PIK3CA, AKT1, PTEN, and FMS-like tyrosine kinase 3 [FLT3]), and evaluate therapeutic approaches, including PI3K/AKT inhibitors and miRNA-based interventions. Furthermore, we identified existing controversies, methodological limitations, and unresolved research gaps. Finally, we emphasize the translational potential of miRNA-targeted therapies and pathway-specific inhibitors, providing insights into their integration into personalized treatment strategies for acute leukemia.
2.Therapeutic Aspects of Mesenchymal Stem Cell-Based Cell Therapy with a Focus on Human Amniotic Epithelial Cells in Multiple Sclerosis: A Mechanistic Review
Reza AREFNEZHAD ; Hossein MOTEDAYYEN ; Ali MOHAMMADI
International Journal of Stem Cells 2021;14(3):241-251
Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS). The mmune system plays an important role in its pathogenesis. Current treatments are unable to cure patients and prevent the progression of MS lesions. Stem cell-based cell therapy has opened a new window for MS treatment. Stem cells regulate immune responses and improve axonal remyelination. Stem cells can be obtained from different origins such as embryonic, neural, bone marrow, and adipose tissues. But yet there is a challenge for the selection of the best cell source for stem cell therapy. Mesenchymal stem cells (MSCs) are a type of stem cell obtained from different origins and have significant immunomodulatory effects on the immune system. The increasing evidence have suggested that umbilical cord and adipose tissue can be a suitable source for isolation of MSCs. Moreover, human amniotic epithelial cells (hAECs) as novel stem cell origins by having immunoregulatory effects, regenerative effects, and less capacity of antigenicity can be a candidate for MS treatment. This review discussed the mechanistic effects of MSCs with a focus on human amniotic epithelial cells, which can be used to treatment and improvement of outcome in MS disease.
3.Therapeutic Aspects of Mesenchymal Stem Cell-Based Cell Therapy with a Focus on Human Amniotic Epithelial Cells in Multiple Sclerosis: A Mechanistic Review
Reza AREFNEZHAD ; Hossein MOTEDAYYEN ; Ali MOHAMMADI
International Journal of Stem Cells 2021;14(3):241-251
Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS). The mmune system plays an important role in its pathogenesis. Current treatments are unable to cure patients and prevent the progression of MS lesions. Stem cell-based cell therapy has opened a new window for MS treatment. Stem cells regulate immune responses and improve axonal remyelination. Stem cells can be obtained from different origins such as embryonic, neural, bone marrow, and adipose tissues. But yet there is a challenge for the selection of the best cell source for stem cell therapy. Mesenchymal stem cells (MSCs) are a type of stem cell obtained from different origins and have significant immunomodulatory effects on the immune system. The increasing evidence have suggested that umbilical cord and adipose tissue can be a suitable source for isolation of MSCs. Moreover, human amniotic epithelial cells (hAECs) as novel stem cell origins by having immunoregulatory effects, regenerative effects, and less capacity of antigenicity can be a candidate for MS treatment. This review discussed the mechanistic effects of MSCs with a focus on human amniotic epithelial cells, which can be used to treatment and improvement of outcome in MS disease.

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