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Öğe Association of clinical features with spike glycoprotein mutations in Iranian COVID-19 patients(MDPI, 2022) Ahangarzadeh, Shahrzad; Yousefi, Alireza; Ranjbar, Mohammad Mehdi; Dabiri, Arezou; Zarepour, Atefeh; Sadeghi, Mahmoud; Heidari, Elham; Mazrui, Fariba; Hosseinzadeh, Majid; Ataei, Behrooz; Zarrabi, Ali; Shariati, Laleh; Javanmard, Shaghayegh HaghjooyBackground: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. Methods: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient's reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. Results: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. Conclusions: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.Öğe 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, AtefehMicroRNAs (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.Öğe Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies(NLM (Medline), 2023) Esmaeili, Yasaman; Mohammadi, Zahra; Khavani, Mohammad; Sanati, Alireza; Shariati, Laleh; Seyedhosseini Ghaheh, Hooria; Bidram, Elham; Zarrabi, AliIntegrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.Öğe 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.Öğe Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study(Elsevier, 2022) Esmaeili, Yasaman; Seyedhosseini Ghaheh, Hooria; Ghasemi, Fahimeh; Shariati, Laleh; Rafienia, Mohammad; Bidram, Elham; Zarrabi, AliWe herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an “on/off” photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity. © 2022 Elsevier B.V.Öğe The importance of SNPs at miRNA binding sites as biomarkers of gastric and colorectal cancers: a systematic review(2022) Hajibabaie, Fatemeh; Abedpoor, Navid; Assareh, Nazanin; Tabatabaiefar, Mohammad Amin; Shariati, Laleh; Zarrabi, AliDysregulated mRNA-miRNA profiles might have the prospective to be used for early diagnosis of gastrointestinal cancers, estimating survival, and predicting response to treatment. Here, a novel biomarker based on miRNAs binding to mRNAs in single nucleotide polymorphism (SNP) sites related to gastrointestinal cancers is introduced that could act as an early diagnosis. The electronic databases used for the recruiting published articles included EMBASE, SCOPUS, Web of Science, and PubMed, based on MESH keywords and PRISMA methodology. Based on the considered criteria, different experimental articles were reviewed, during which 15 studies with the desired criteria were collected. Accordingly, novel biomarkers in prediction, early prognosis, and diagnosis of gastrointestinal cancers were highlighted. Moreover, it was found that 20 SNP sites and 16 miRNAs were involved in gastrointestinal cancers, with altered expression patterns associated with clinicopathological and demographic data. The results of this systematic study revealed that SNPs could affect the binding of miRNAs in the SNP sites that might play a principal role in the progression, invasion, and susceptibility of gastrointestinal cancers. In addition, it was found that the profiles of SNPs and miRNAs could serve as a convenient approach for the prognosis and diagnosis of gastric and colorectal cancers.
