Sharif Digital Repository

Conformational diseases have been investigated extensively in recent years; as a result, a number of drug candidates have been introduced as amyloid inhibitors; however, no effective therapies have been put forward. RS-0406 with pyridazine as its core chemical structure has so far shown promising results in inhibiting amyloid formation. In the present work, using molecular dynamics, we undertook the investigation of RS-0406 interactions with U-shaped Aβ1−42 and Aβ1−40 pentamers, Aβ1−42 monomers, and double-horseshoe-like Aβ1−42. To set better parameters for the small molecule, experimental and computational log P values were obtained. In addition, an analogue of RS-0406 was also simulated... 

The cell membrane is responsible for the transportation of heat between inside and outside the cell. Whether the thermal properties of the cell membrane are affected by the cholesterol concentration or the membrane proteins has not been investigated so far. Although the experimental measurement of the membrane thermal conductivity was not available until very recently, computational methods have been widely used for this purpose. In this study, we carry out molecular dynamics simulations to investigate the relation between the concentration of cholesterol and the thermal conductivity of a model membrane. Our results suggest an increase in the membrane thermal conductivity upon increasing the... 

SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans... 

Since amyloid beta fibrillation (AβF) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of Aβ fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the AβF process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the AβF process by adsorption of amyloid monomers. The inhibitory effect of the GO sheet was increased when we increase the concentration from 10% (in vitro; stimulated media) to 100% (in vivo; stimulated media). Conclusion: our results revealed that GO and their surface... 

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... 

Gold nanoparticles are potentially very attractive components for therapeutic delivery since they can be synthesized with any diameter from 1 to 200 nm to carry a payload of therapeutic molecules into a cell without triggering an immune response. Gold nanoparticles must undergo surface transformations before coupling to therapeutic molecules to become eligible for this purpose. It is now more understood that amine groups can bind to gold nanoparticles strongly, which has enabled surface modification of gold nanoparticles with amino acid lysine through its amine group. These lysine capped gold nanoparticles can further be coupled to therapeutic molecules for delivery purposes. In this study... 

Background: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic... 

Protein fibrillation process (e.g., from amyloid beta (Aβ) and α-synuclein) is the main cause of several catastrophic neurodegenerative diseases such as Alzheimer's and Parkinson diseases. During the past few decades, nanoparticles (NPs) were recognized as one of the most promising tools for inhibiting the progress of the disease by controlling the fibrillation kinetic process; for instance, gold NPs have a strong capability to inhibit Aβ fibrillations. It is now well understood that a layer of biomolecules would cover the surface of NPs (so called "protein corona") upon the interaction of NPs with protein sources. Due to the fact that the biological species (e.g., cells and amyloidal... 

von Willebrand factor (VWF) is a naturally collapsed protein that participates in primary haemostasis and coagulation events. The clotting process is triggered by the adsorption and conformational changes of the plasma VWFs localized to the collagen fibres found near the site of injury. We develop coarse-grained models to simulate the adsorption dynamics of VWF flowing near the adhesive collagen fibres at different shear rates and investigate the effect of factors such as interaction and cooperativity of VWFs on the success of adsorption events. The adsorption probability of a flowing VWF confined to the receptor field is enhanced when it encounters an adhered VWF in proximity to the... 

Monitoring the ratio of 40- and 42-residue amyloid β peptides (i.e., Aβ40 and Aβ42) in human plasma is considered one of the hallmarks of detection of the early stage of Alzheimer's disease (AD). Therefore, development of a specific, yet non-antibody-based method for simultaneous detection of Aβ40 and Aβ42 may have considerable clinical applications. Here, we developed a 'nanoparticle-based colorimetric sensor array' utilizing label-free gold and silver nanoparticles for visual detection of Aβ42 and Aβ40. Different aggregation behaviors of nanoparticles through their conjugation with Aβ42 and Aβ40 followed by the coordination of Aβ42 and Aβ40 with Cu(ii) led to diverse spectral and color... 

In this study, the effectiveness of PASylation in enhancing the potency and plasma half-life of pharmaceutical proteins has been accredited as an alternative technique to the conventional methods such as PEGylation. Proline, alanine, and serine (PAS) chain has shown some advantages including biodegradability improvement and plasma half-life enhancement while lacking immunogenicity or toxicity. Although some experimental studies have been performed to find the mechanism behind PASylation, the detailed mechanism of PAS effects on the pharmaceutical proteins has remained obscure, especially at the molecular level. In this study, the interaction of interferon α-2a (IFN) and PAS chain is... 

Systemic inflammation biomarkers have been associated with risk of cardiovascular morbidity and mortality. We aimed to clarify associations of acute exposure to particulate matter (PM10(PM < 10 μm), PM2.5-10(PM 2.5–10 μm), PM2.5(PM < 2.5 μm), PM1-2.5(PM 1–2.5 μm), and PM1 (PM < 1 μm)) with systemic inflammation using panels of elderly subjects and healthy young adults. We followed a panel of 44 nonsmoking elderly subjects living in a retirement home and a panel of 40 healthy young adults living in a school dormitory in Tehran city, Iran from May 2012 to May 2013. Blood biomarkers were measured one every 7–8 weeks and included white blood cells (WBC), high sensitive C-reactive protein... 

Surface functionality of nanoparticles has been pivotal in defining interactions of nanoparticles and biomolecules. To explore various functionalities on the surface of nanoparticle through a facile procedure, various carbon-based nanoparticles, modified with a specific natural amino acid, were synthesized; the amino acids were chosen in order that almost all classes of amino acids were included. After characterizations of the nanoparticles using several spectroscopic methods, the effects of surface modification of nanoparticles were examined against amyloid formation, exploiting insulin as a model amyloidogenic polypeptide. Although most amino acids afforded carbon nanoparticles, only... 

Background: Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to oligodendrocytes. However, the limitation in nerve tissue acces-sibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging. Purpose: In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced. Materials and Methods: In order to achieve a sustained release of T3, this factor was... 

The delivery of growth factors is often challenging due to their short half-life, low stability, and rapid deactivation. In native tissues, the sulfated residual of glycosaminoglycan (GAG) polymer chains of proteoglycans immobilizes growth factors through the proteoglycans'/proteins' complexation with nanoscale organization. These biological assemblies can influence growth factor-cell surface receptor interactions, cell differentiation, cell-cell signaling, and mechanical properties of the tissues. Here, we introduce a facile procedure to prepare novel biomimetic proteoglycan nanocarriers, based on naturally derived polymers, for the immobilization and controlled release of growth factors....