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    Dynamics of Protein-Embedded Vesicles in Simple Shear Flow

    , M.Sc. Thesis Sharif University of Technology Hoore, Masoud (Author) ; Jalali, Mir Abbas (Supervisor) ; Khoshnood, Atefeh (Co-Advisor)
    Abstract
    Studying the dynamics of vesicles in simple shear flow is the first step to decipher the dynamics of cells in flows or the motion of vesicle-based nanoparticles in vessels for drug delivery. The deformation of vesicle in shear flow changes the permeability of its membrane and may lead to its rupture, both of which correlate with the transportation of vesicle cargos to their environment, especially important in drug delivery. The deformation of vesicles in shear flow not only depends on the physical properties of the whole system, such as temperature, but also on the mechanical properties of three media: vesicle membrane plus vesicle’s inner and outer fluid. The effect of the mechanical... 

    Protein Aggregation in Biological Membrane

    , M.Sc. Thesis Sharif University of Technology Mobalegh Tohid, Sajedeh (Author) ; Jalali, Mir Abbas (Supervisor) ; Ejtehadi, Mohammad Reza (Co-Advisor)
    Abstract
    Aggregation of membrane proteins plays a determinative role in many biological processes، such as signal transduction, cell division and endocytosis. In the present study, we have investigated the interaction between proteins in vesicles by means of coarse-grained molecular dynamics simulations. In the first step, a number of periodic lipid bilayers were simulated and their physical properties were calculated. Then, bilayers were immersed in water and converted into spherical vesicles via a selforganizing process . Finally two proteins were embedded into the vesicle and the potential of mean force (PMF) respect to the angle between them was obtained using umbrella sampling. This process was... 

    Review on alzheimer's disease: inhibition of amyloid beta and tau tangle formation

    , Article International Journal of Biological Macromolecules ; Volume 167 , 2021 , Pages 382-394 ; 01418130 (ISSN) Ashrafian, H ; Hadi Zadeh, E ; Hasan Khan, R ; Sharif University of Technology
    Elsevier B.V  2021
    Abstract
    It is reported that approximately 40 million people are suffering from dementia, globally. Dementia is a group of symptoms that affect neurons and cause some mental disorders, such as losing memory. Alzheimer's disease (AD) which is known as the most common cause of dementia, is one of the top medical care concerns across the world. Although the exact sources of the disease are not understood, is it believed that aggregation of amyloid-beta (Aβ) outside of neuron cells and tau aggregation or neurofibrillary tangles (NFTs) formation inside the cell may play crucial roles. In this paper, we are going to review studies that targeted inhibition of amyloid plaque and tau protein tangle formation,... 

    Discovery of a tetracyclic indole alkaloid that postpones fibrillation of hen egg white lysozyme protein

    , Article International Journal of Biological Macromolecules ; Volume 183 , 2021 , Pages 1939-1947 ; 01418130 (ISSN) Ashrafian, H ; Zadeh, E.H ; Tajbakhsh, M ; Majid, N ; Srivastava, G.N ; Khan, R.H ; Sharif University of Technology
    Elsevier B.V  2021
    Abstract
    Protein aggregation, such as amyloid fibril formation, is molecular hallmark of many neurodegenerative disorders including Alzheimer's, Parkinson's, and Prion disease. Indole alkaloids are well-known as the compounds having the ability to inhibit protein fibrillation. In this study, we experimentally and computationally have investigated the anti-amyloid property of a derivative of a synthesized tetracyclic indole alkaloid (TCIA), possessing capable functional groups. The fibrillation reaction of Hen White Egg Lysozyme (HEWL) was performed in absence and presence of the indole alkaloid. For quantitative analysis, we used Thioflovin T binding assay which showed ~50% reduction in fibril... 

    Identification of an aspidospermine derivative from borage extract as an anti-amyloid compound: A possible link between protein aggregation and antimalarial drugs

    , Article Phytochemistry ; Volume 140 , 2017 , Pages 134-140 ; 00319422 (ISSN) Kalhor, H. R ; Ashrafian, H ; Sharif University of Technology
    Elsevier Ltd  2017
    Abstract
    A number of human diseases, including Alzheimer's and Parkinson's have been linked to amyloid formation. To search for an anti-amyloidogenic product, alkaloid enriched extract from borage leaves was examined for anti-amyloidogenic activity using Hen Egg White Lysozyme (HEWL) as a model protein. After isolation of the plant extract using rHPLC, only one fraction indicated a significant bioactivity. TEM analysis confirmed a remarkable reduction of amyloid fibrils in the presence of the bioactive fraction. To identify the effective substance in the fraction, mass spectrometry, FTIR, and NMR were performed. Our analyses determined that the bioactive compound as... 

    Development of a novel nano-sized anti-VEGFA nanobody with enhanced physicochemical and pharmacokinetic properties

    , Article Artificial Cells, Nanomedicine and Biotechnology ; Volume 46, Issue 7 , 2018 , Pages 1402-1414 ; 21691401 (ISSN) Khodabakhsh, F ; Norouzian, D ; Vaziri, B ; Ahangari Cohan, R ; Sardari, S ; Mahboudi, F ; Behdani, M ; Mansouri, K ; Mehdizadeh, A ; Sharif University of Technology
    Abstract
    Since physiological and pathological processes occur at nano-environments, nanotechnology has considered as an efficient tool for designing of next generation specific biomolecules with enhanced pharmacodynamic and pharmacodynamic properties. In the current investigation, by control of the size and hydrodynamic volume at the nanoscale, for the first time, physicochemical and pharmacokinetic properties of an anti-VEGFA nanobody was remarkably improved by attachment of a Proline-Alanine-Serine (PAS) rich sequence. The results elucidated unexpected impressive effects of PAS sequence on physicochemical properties especially on size, hydrodynamics radius, and even solubility of nanobody. CD... 

    Design of peptide-based inhibitor agent against amyloid-β aggregation: Molecular docking, synthesis and in vitro evaluation

    , Article Bioorganic Chemistry ; Volume 102 , September , 2020 Jokar, S ; Erfani, M ; Bavi, O ; Khazaei, S ; Sharifzadeh, M ; Hajiramezanali, M ; Beiki, D ; Shamloo, A ; Sharif University of Technology
    Academic Press Inc  2020
    Abstract
    Formation of the amyloid beta (Aβ) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. β-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. According to the obtained interactions and binding energy from docking, the best-designed peptide (D-GABA-FPLIAIMA) was chosen and... 

    Modeling, simulation, and employing dilution–dialysis microfluidic chip (DDMC) for heightening proteins refolding efficiency

    , Article Bioprocess and Biosystems Engineering ; Volume 41, Issue 5 , 2018 , Pages 707-714 ; 16157591 (ISSN) Kashanian, F ; Masoudi, M. M ; Shamloo, A ; Habibi Rezaei, M ; Moosavi Movahedi, A. A ; Sharif University of Technology
    Springer Verlag  2018
    Abstract
    Miniaturized systems based on the principles of microfluidics are widely used in various fields, such as biochemical and biomedical applications. Systematic design processes are demanded the proper use of these microfluidic devices based on mathematical simulations. Aggregated proteins (e.g., inclusion bodies) in solution with chaotropic agents (such as urea) at high concentration in combination with reducing agents are denatured. Refolding methods to achieve the native proteins from inclusion bodies of recombinant protein relying on denaturant dilution or dialysis approaches for suppressing protein aggregation is very important in the industrial field. In this paper, a modeling approach is... 

    Removal of bisphenol A in aqueous solution using magnetic cross-linked laccase aggregates from Trametes hirsuta

    , Article Bioresource Technology ; Volume 306 , 2020 Sadeghzadeh, S ; Ghobadi Nejad, Z ; Ghasemi, S ; Khafaji, M ; Borghei, S. M ; Sharif University of Technology
    Elsevier Ltd  2020
    Abstract
    Enzymatic removal of Bisphenol A (BPA), acknowledged as an environmentally friendly approach, is a promising method to deal with hard degradable contaminants. However, the application of “enzymatic treatment” has been limited due to lower operational stability and practical difficulties associated with recovery and recycling. Enzyme immobilization is an innovative approach which circumvents these drawbacks. In this study, laccase from Trametes hirsuta was used for BPA removal. Amino-functionalized magnetic Fe3O4 nanoparticles were synthesized via the co-precipitation method followed by surface modification with (3-aminopropyl)trimethoxysilane (APTMS). The as-prepared nanoparticles were... 

    Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy

    , Article Biophysical Reviews ; Volume 11, Issue 6 , 2019 , Pages 901-925 ; 18672450 (ISSN) Jokar, S ; Khazaei, S ; Behnammanesh, H ; Shamloo, A ; Erfani, M ; Beiki, D ; Bavi, O ; Sharif University of Technology
    Springer  2019
    Abstract
    Alzheimer’s disease (AD) is an irreversible neurological disorder that progresses gradually and can cause severe cognitive and behavioral impairments. This disease is currently considered a social and economic incurable issue due to its complicated and multifactorial characteristics. Despite decades of extensive research, we still lack definitive AD diagnostic and effective therapeutic tools. Consequently, one of the most challenging subjects in modern medicine is the need for the development of new strategies for the treatment of AD. A large body of evidence indicates that amyloid-β (Aβ) peptide fibrillation plays a key role in the onset and progression of AD. Recent studies have reported...