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Öğe Exploring the evolution of tissue engineering strategies over the past decade: From cell-based strategies to gene-activated matrix(Elsevier, 2023) Esmaeili, Yasaman; Bidram, Elham; Bigham, Ashkan; Atari, Mehdi; Azadani, Reyhaneh Nasr; Tavakoli, Mohamadreza; Salehi, SaeidehThe advancement of tissue engineering for regenerating injured tissues and organs has progressed significantly in recent years. Various techniques have been used to modify the cells' microenvironments in the targeted tissue via their extracellular environment for achieving these aims. The 3D structured scaffolds alone or combined with bioactive molecules or genes and cells hold great promise for the development of functional engineered tissues. As an emerging and state-of-the-art technology in this field, integrating tissue engineering and gene therapy, known as gene-activated matrix (GAM), has gained immense attention as a promising approach for restoring damaged or dysfunctional tissues' function and structure. Nonetheless, fabricating GAMs with low cytotoxicity, high transfection efficiency, and long-term gene delivery efficiency is still challenging. Here we provide a complete overview of different tissue engineering approaches and their ongoing preclinical research trials. Moreover, the GAM strategy with a focus on gene-activated matrix development, faithful application, and future prospects as a tissue repair and regeneration replacement is assayed. The challenges and future research prospects in regenerative medicine are also presented. Eventually, we propose that GAMs offer a basic mechanistic infrastructure for tissue engineering to pave the way for clinical translation and achieve personalized regenerative medicine.Öğe Exploring the evolution of tissue engineering strategies over the past decade: From cell-based strategies to gene-activated matrix (vol 81, pg 137, 2023)(Elsevier, 2023) Esmaeili, Yasaman; Bidram, Elham; Bigham, Ashkan; Atari, Mehdi; Azadani, Reyhaneh Nasr; Tavakoli, Mohamadreza; Salehi, Saeideh[Abstract Not Available]Öğe Fabrication of 3D porous polyurethane-graphene oxide scaffolds by a sequential two-step processing for non-load bearing bone defects(Iop Publishing Ltd, 2024) Bagheri, Fatemeh; Saudi, Ahmad; Bidram, Elham; Asefnejad, Azadeh; Sanati, Alireza; Zarrabi, Ali; Rafienia, MohammadBone defects as a common orthopedic disease lead to severe pains over a long period. Scaffolds are novel approaches in tissue engineering to treat bone problems and deal with their challenges. Here, 3D porous polyurethane (PU) scaffolds containing graphene oxide (GO) with different percentages (0, 0.1, 0.3, and 0.5 wt%) were developed through a combination of freeze-drying and salt etching techniques for bone tissue engineering applications. The morphologies of scaffolds, physicochemical properties, the degree of crystallinity, and hydrophilicity were evaluated by SEM, FTIR, XRD, and water contact angle assay, respectively. The porosity, degradation behavior, compressive strength, and elastic modulus of 3D porous scaffolds were also determined. To assess the scaffold bioactivity, the morphology of the deposited calcium phosphate layer on the scaffold with macro-structure was evaluated by SEM images. The viability and adhesion of MG63 osteoblast-like cells cultured on the fabricated scaffolds were examined by MTT assay and SEM images, respectively. The results show that adding GO particles not only had no effect on the interconnectivity and porosity of 3D porous macroscopic structures of neat PU but also smaller and more uniformed microscopically pores were obtained. The crystallinity, water contact angle, and weight loss of scaffolds increased as the higher GO concentrations were employed. Followed by increasing GO contents from 0 to 0.5 wt%, the compressive strength and Young's modulus were increased by 232% and 245%, respectively. The bioactivity of scaffolds was fostered as GO concentration increased. Although, the MTT assay proved the biocompatibility of PU scaffolds containing 0.1 and 0.3 wt% GO, the samples loaded with 0.5 GO had a negative impact on the viability of MG63 cell lines. In conclusion, the present study demonstrates a high potential of PU scaffolds loaded with 0.1 and 0.3 wt% GO particles in bone tissue engineering applications.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 Penicillin and oxacillin loaded on pegylated-graphene oxide to enhance the activity of the antibiotics against methicillin-resistant staphylococcus aureus(MDPI, 2022) Zarepour, Atefeh; Zarrabi, Ali; Tabar, Mohadeseh Mohammadi; Khaleghi, Moj; Bidram, ElhamInfectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol (GO-PEG) nano-platform was synthesized and penicillin and oxacillin, two antibiotics that are ineffective against Methicillin-resistant S. aureus (MRSA), were loaded on it to improve their effectiveness. The nanocomposites were characterized using FTIR, XRD, UV-Vis, FE-SEM/EDX, and Zeta potential analyses, followed by an evaluation of their antibacterial activity toward MRSA. Based on the results, drug loaded GO-PEG nanocomposites with loading efficiencies of 81% and 92% for penicillin and oxacillin, respectively, were successfully synthesized. They showed a controlled release within six days. The zeta potential of GO-PEG-oxacillin and penicillin was -13 mV and -11 mV, respectively. The composites showed much more activity against MRSA (80-85% inhibition) in comparison to GO-PEG (almost 0% inhibition) and pure antibiotics (40-45% inhibition). SEM images of MRSA treated with GO-PEG-antibiotics showed a deformation in the structure of bacterial cells, which led to the collapse of their intracellular components. These results demonstrate the effectiveness of utilizing the GO-based nanoplatforms in enhancing the antibacterial activity of the antibiotics.Öğe Smartphone-assisted lab-in-a-tube device using gold nanocluster-based aptasensor for detection of MUC1-overexpressed tumor cells(Elsevier, 2023) Sanati, Alireza; Esmaeili, Yasaman; Khavani, Mohammad; Bidram, Elham; Rahimi, Azadeh; Dabiri, Arezou; Rafienia, MohammadDeveloping smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor.Öğe Targeting autophagy, oxidative stress, and ER stress for neurodegenerative diseases treatment(2022) Esmaeili, Yasaman; Yarjanli, Zahra; Pakniya, Fatemeh; Bidram, Elham; Los, Marek J; Eshraghi, Mehdi; Klionsky, Daniel J; Ghavami, Saeid; Zarrabi, AliProtein homeostasis is a vital process for cell function and, therefore, disruption of the molecular mechanisms involved in this process, such as autophagy, may contribute to neurodegenerative diseases (NDs). Apart from autophagy disruption, excess oxidative stress and endoplasmic reticulum (ER) stress are additional main molecular mechanisms underlying neurodegeneration, leading to protein aggregation, and mitochondrial dysfunction. Notably, these primary molecular processes are interconnected pathways which have synergistic effects on each other. Therefore, we propose that targeting of the crosstalk between autophagy, oxidative stress and ER stress simultaneously may play a critical role in healing NDs. NeuroNanoTechnology, as a revolutionized approach, in combination with an in-silico strategy, holds great promise for developing de-novo structures for targeting and modulating neuro-molecular pathways. Accordingly, this review outlines the contributions of autophagy, oxidative stress, and ER stress in neurodegenerative conditions along with a particular focus on the crosstalk among these pathways. Furthermore, we provide a comprehensive discussion on the potential of nanomaterials to target this crosstalk and suggest this potential as a promising opportunity in neuroprotection.