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    Crosstalk of Transcriptional Regulators of Adaptive Immune System and microRNAs: An Insight into Differentiation and Development
    (Mdpi, 2023) Boshtam, Maryam; Rahimmanesh, Ilnaz; Shariati, Laleh; Najaflu, Malihe; Khanahmad, Hossein; Mirian, Mina; Zarepour, Atefeh
    MicroRNAs (miRNAs), as small regulatory RNA molecules, are involved in gene expression at the post-transcriptional level. Hence, miRNAs contribute to gene regulation of various steps of different cell subsets' differentiation, maturation, and activation. The adaptive immune system arm, which exhibits the most specific immune responses, is also modulated by miRNAs. The generation and maturation of various T-cell subsets concomitant with B-cells is under precise regulation of miRNAs which function directly on the hallmark genes of each cell subset or indirectly through regulation of signaling pathway mediators and/or transcription factors involved in this maturation journey. In this review, we first discussed the origination process of common lymphocyte progenitors from hematopoietic stem cells, which further differentiate into various T-cell subsets under strict regulation of miRNAs and transcription factors. Subsequently, the differentiation of B-cells from common lymphocyte progenitors in bone marrow and periphery were discussed in association with a network of miRNAs and transcription factors.
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    Gene editing-based technologies for beta-hemoglobinopathies treatment
    (MDPI, 2022) Rahimmanesh, Ilnaz; Boshtam, Maryam; Kouhpayeh, Shirin; Khanahmad, Hossein; Dabiri, Arezou; Ahangarzadeh, Shahrzad; Esmaeili, Yasaman; Bidram, Elham; Vaseghi, Golnaz; Haghjooy, Shaghayegh; Shariati, Laleh; Zarrabi, Ali; Varma, Rajender S.
    Simple Summary: ?-thalassemia syndromes are clinically and genetically heterogeneous blood disorders presented by ?-chain deficiency in hemoglobin production. Despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, which have been recently applied to improve ?-thalassemia symptoms. Nevertheless, several obstacles, such as off-target effects, protospaceradjacent motif requirement, efficient gene transfer and expression methods, DNA-damage toxicity, and immunotoxicity issues still need to be addressed in order to improve the safety and efficacy of the gene editing approaches. Hence, additional efforts are needed to address these problems, evaluate the safety of genome editing tools at the clinical level and follow the outcomes of gene editing tools-mediated therapeutic approaches in related patients. Abstract: Beta (?)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the ?-globin chains in hemoglobin structure. Traditional treatment for ?-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat–Cas-associated nucleases. These tools have concentrated on ?- or ?-globin addition, regulating the transcription factors involved in expression of endogenous ?-globin such as KLF1, silencing of ?-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for ?-thalassemia treatment and paving the way for patients’ therapy.