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    Design and physicochemical characterization of lysozyme loaded niosomal formulations as a new controlled delivery system

    , Article Pharmaceutical Chemistry Journal ; Volume 53, Issue 10 , 2020 , Pages 921-930 Sadeghi, S ; Ehsani, P ; Cohan, R. A ; Sardari, S ; Akbarzadeh, I ; Bakhshandeh, H ; Norouzian, D ; Sharif University of Technology
    Springer  2020
    Abstract
    Lysozyme loaded niosomes containing various molar ratios of two kinds of surfactants were prepared and the properties of these niosomal formulations were studied. The results revealed that the size of niosomes varied between 240.06 ± 32.41 and 895.2 ± 20.84 nm. Formulations with the lowest size and no precipitation had entrapment efficiencies ranging from 60.644 ± 3.310 to 66.333 ± 1.98%. Their controlled release profiles after 48 h were 15.67, 20.67 and 31.50%. After 2 months, the most stable formulation in terms of size, PDI, zeta potential, and entrapment efficiency was used to study the secondary structures of lysozyme in niosomal and free forms. Lysozyme loaded niosome and lysozyme... 

    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... 

    The Use of Flavin Reductase Enzyme as Biocatalyst in Promiscuous Catalyzing Organic Reactions and Investigating Amyloid Inhibition in Proteins Using Aromatic Compounds

    , M.Sc. Thesis Sharif University of Technology Masihzadeh, Zahra (Author) ; Kalhor, Hamid Reza (Supervisor)
    Abstract
    Enzymes are proteins that carry out chemical reactions in the form of chemo, stereo, and regioselective under mild conditions. One of the characteristics of enzymes is that they perform a specific chemical reaction on a selective substrate and under specific environmental conditions. However, in recent years, a number of enzymes have been identified to display promiscous behavior. This promiscousity includes catalytic activity, variety of substrates, and environmental conditions. Promiscous activities of enzymes can be a good starting point for creating new and more favorable engineered pathways for the production of chemical and medicinal drugs. One of the aims of this project is to exploit... 

    Investigating reliable conditions for hewl as an amyloid model in computational studies and drug interactions

    , Article Journal of Chemical Information and Modeling ; Volume 59, Issue 12 , 2019 , Pages 5218-5229 ; 15499596 (ISSN) Kalhor, H. R ; Jabbary, M ; Sharif University of Technology
    American Chemical Society  2019
    Abstract
    A number of conformational diseases in humans have been associated with protein/peptide fibrillation known as amyloid. Although extensive studies have been conducted in understanding the molecular basis of amyloid formation, a detailed mechanism is still missing. Experimentally, HEWL (hen egg white lysozyme) has been exploited ubiquitously as a model protein for amyloid fibrillation and drug inhibition. However, computational studies investigating fibril formation of HEWL have been a difficult task to perform mainly due to high stability of lysozymes and the absence of crystal structures of HEWL fibril oligomers. In this study, we have examined various conditions of HEWL amyloid formation... 

    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... 

    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... 

    Creating Random Mutations on The Human Transglutaminase 2 Gene and Lysozyme Gene to Increase The Solubility of the Enzymes in order to Perform Promiscuous Organic Reactions Using The Recombinant Enzymes

    , M.Sc. Thesis Sharif University of Technology Moghaddasi, Ahmad (Author) ; Kalhor, Hamid Reza (Supervisor)
    Abstract
    Transglutaminase 2 enzyme is expressed in various parts of the human body and is present in almost all tissue cells. The function of this enzyme is multiple and it catalyzes different reactions depending on where it is located in the cell. The most important activities of this enzyme are: isopeptide bond formation between the side chains of two proteins (transamidation reaction), diamidation reaction (hydrolysis of amide bond), esterification, kinase activity. The hen egg white lysozyme protein is another natural antimicrobial protein that has been extensively studied. The muramidase activity of egg white lysozyme against highly gram-positive bacteria is well known, and this property has... 

    Prediction of the partition coefficients of biomolecules in polymer-polymer aqueous two-phase systems using the artificial neural network model

    , Article Particulate Science and Technology ; Volume 28, Issue 1 , 2010 , Pages 67-73 ; 02726351 (ISSN) Pazuki, G. R ; Taghikhani, V ; Vossoughi, M ; Sharif University of Technology
    Abstract
    In this work, an artificial neural network model was used to obtain the partition coefficients of biomolecules in polymer-polymer aqueous two-phase systems. In the artificial neural network, the partition coefficient of a biomolecule depends on the difference between concentrations of poly (ethylene glycol), dextran in the top and bottom phases, temperature and molecular weights of poly (ethylene glycol), dextran, and the biomolecule. The network topology is optimized and the (6-1-1) architecture is found using optimization of an objective function with sequential quadratic programming (SQP) method for 450 experimental data points. The results obtained from the neural network of the... 

    Amyloid fibril reduction through covalently modified lysine in HEWL and insulin

    , Article Archives of Biochemistry and Biophysics ; Volume 727 , 2022 ; 00039861 (ISSN) Rezaei, M ; Kalhor, H. R ; Sharif University of Technology
    Academic Press Inc  2022
    Abstract
    Proteins possess a variety of nucleophiles, which can carry out different reactions in the functioning cells. Proteins endogenously and synthetically can be modified through their nucleophilic sites. The roles of these chemical modifications have not been completely revealed. These modifications can alter the protein folding process. Protein folding directly affects the function of proteins. If an error in protein folding occurs, it may cause protein malfunction leading to several neurodegenerative disorders such as Alzheimer's and Parkinson's. In this study, Hen Egg White Lysozyme (HEWL) and bovine insulin, as model proteins for studying the amyloid formation, were covalently attached with... 

    Core-sheath gelatin based electrospun nanofibers for dual delivery release of biomolecules and therapeutics

    , Article Materials Science and Engineering C ; Volume 108 , 2020 Zandi, N ; Lotfi, R ; Tamjid, E ; Shokrgozar, M. A ; Simchi, A ; Sharif University of Technology
    Elsevier Ltd  2020
    Abstract
    Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and... 

    Synthesis and structure activity relationship of pyridazine-based inhibitors for elucidating the mechanism of amyloid inhibition

    , Article Chemical Research in Toxicology ; Volume 31, Issue 10 , 2018 , Pages 1092-1104 ; 0893228X (ISSN) Kalhor, H. R ; Nazari Khodadadi, A ; Sharif University of Technology
    American Chemical Society  2018
    Abstract
    Conformational diseases, constituting a large number of diseases, have been connected with protein misfolding, leading to aggregation known as amyloid fibrils. Mainly due to the lack of detailed molecular mechanisms, there has not been an effective drug to combat amyloid-associated diseases. Recently, a small organic pyridazine-based molecule (RS-0406) has shown significant reductions in amyloid fibrils in both in vitro and in vivo animal studies. However, no information on molecular details of inhibition for the small molecule has been reported. In this work, we have decided to explore structure-activity relationship of pyridazine-based compounds to investigate structural parameters for... 

    Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes

    , Article AAPS Journal ; Volume 19, Issue 3 , 2017 , Pages 652-668 ; 15507416 (ISSN) Morales, J. O ; Fathe, K. R ; Brunaugh, A ; Ferrati, S ; Li, S ; Montenegro Nicolini, M ; Mousavikhamene, Z ; McConville, J. T ; Prausnitz, M. R ; Smyth, H. D. C ; Sharif University of Technology
    Springer New York LLC  2017
    Abstract
    Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the...