Sharif Digital Repository

The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver-targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect... 

Despite a diverse range of active pharmaceutical agents currently at our disposal, high morbidity rate diseases continue to pose a major health crisis globally. One of the important parameters in this regard is the controlled cargo delivery at desired sites. Among a variety of synthetic and natural macromolecular systems, chitosan, an abundant biopolymer, offers a platform for tailored architectures that could have high loading capacity of cargo, target and deliver. Stimuli directed accumulation of vehicles and drug release is an area of direct relevance to biomedical applications. In this review, we highlight essential characteristics of modified chitosan that present themselves for... 

The thermophilic bacterium Nocardia otitidiscaviarum strain TSH1, originally isolated in our laboratory from a petroindustrial wastewater contaminated soil in Iran, grows at 50 °C on a broad range of hydrocarbons. Transformation of naphthalene by strain TSH1 which is able to use this two ring-polycyclic aromatic hydrocarbon (PAH) as a sole source of carbon and energy was investigated. The metabolic pathway was elucidated by identifying metabolites, biotransformation studies and monitoring enzyme activities in cell-free extracts. The identification of metabolites suggests that strain TSH1 initiates its attack on naphthalene by dioxygenation at its C-1 and C-2 positions to give... 

Prostate cancer (PCa), the second most malignant neoplasm in men, is also the fifth leading cause of cancer-related deaths in men globally. Unfortunately, this malignancy remains largely asymptomatic until late-stage emergence when treatment is limited due to the lack of effective metastatic PCa therapeutics. Due to these limitations, early PCa detection through prostate-specific antigen (PSA) screening has become increasingly important, resulting in a more than 50% decrease in mortality. Conventional assays for PSA detection, such as enzyme-linked immunosorbent assay (ELISA), are labor intensive, relatively expensive, operator-dependent and do not provide adequate sensitivity.... 

The global COVID-19 pandemic has affected the world’s population by causing changes in behavior, such as social distancing, masking, restricting people’s movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of... 

The employment of tissue engineering scaffolds in the reconstruction of the damaged bone tissues has shown remarkable promise since they significantly facilitate the healing process. Fabrication of highly porous biocompatible scaffolds with sufficient mechanical strength is still challenging. In this regard, polymers have been widely utilized to construct three-dimensional (3D) porous scaffolds due to their excellent processability and biocompatibility. However, insufficient mechanical strength and inappropriate degradation rate of the monophasic polymer scaffolds in the bone regeneration process, as the main challenges, limit their extensive clinical application. The incorporation of... 

Background: Hepatitis B virus surface antigen (HBsAg) is an important protein in both diagnosis and prevention of hepatitis B infection. In the current study, a piezoelectric immunosensor based on antibody-antigen interaction was designed to detect HBsAg. A quartz crystal microbalance system was employed to detect antibody-antigen interaction. Methods: At first, an oscillator was designed to measure the resonant frequency affected by the reactants using IC 74LVC1GX04. Antibody against HBsAg was immobilized on 10 MHz AT-cut quartz crystal. The surface modifications were monitored by atomic force microscopy (AFM) and contact angle measurements. Different concentrations of antibody were used... 

Binding of the SARS-CoV-2 S-glycoprotein to cell receptors is vital for the entry of the virus into cells and subsequent infection. ACE2 is the main cell receptor for SARS-CoV-2, which can attach to the C-terminal receptor-binding domain (RBD) of the SARS-CoV-2 S-glycoprotein. The GRP78 receptor plays an anchoring role, which attaches to the RBD and increases the chance of other RBDs binding to ACE2. Although high levels of reactive oxygen and nitrogen species (RONS) are produced during viral infections, it is not clear how they affect the RBD structure and its binding to ACE2 and GRP78. In this research, we apply molecular dynamics simulations to study the effect of oxidation of the highly... 

Open-pore titanium scaffolds were fabricated by sintering of compressed mixtures of TiH1.924 and urea. Spherical and irregular shaped space holders were used to investigate the effect of pore shape on cellular behavior. After removal of the space holder, the shape of the spacers was replicated to the pores. Average diameter of the pores was in the range of 300-600 lm. SEM images showed that titanium hydride resulted in higher surface roughness and larger micro porosities than pure titanium. In vitro evaluationswere carried out by using MTT assay, measuring alkaline phosphatase activity and alizarin red staining in flow perfusion bioreactor for cell culture. Observations revealed excellent... 

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational... 

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal... 

The clarification of rough non-alcoholic beer (RNAB) and diluted malt extract (DME) was investigated in a pilot plant consisting of a tubular ceramic membrane with nominal pore diameter of 0.45μm. The results of the primary experiments show that the concentration of suspended particles in the RNAB (∼0.05kg/m3) and DME (∼0.2kg/m3) correlates proportionally to turbidity (in NTU) with the factor of 4.45×10-4 (kgm-3NTU-1). During cross-flow microfiltration (CFMF), flux declined drastically with time due to fouling mechanisms and propensity. According to the characterizing curve of log(d2t/dV2) versus log(dt/dV), fouling is initiated by penetration of aggregates through the membrane surface,... 

The oxidation-reduction (redox)–responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic–hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations higher than the critical micelle concentration (CMC)... 

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... 

Interaction between intracellular dynamics and extracellular matrix (ECM) generally occurred into very thin fragment of moving cell, namely lamellipodia, enables all movable cells to crawl on ECM. In fast-moving cells such as fish Keratocytes, Lamellipodia including most cell area finds a fan-like shape during migration, with a variety of aspect ratio function of fish type. In this work, our purpose is to present a novel and more complete two-dimensional continuum mathematical model of actomyosin-cytosolic two-phase flow of a self-deforming Keratocyte with circular spreaded to steady fan-like shape. In the new approach, in addition to the two-phase flow of the F-actin and cytosol, the... 

In this study, lyophilized advanced platelet rich fibrin (A-PRF) was used in combination with collagen-chitosan membrane for the first time to combine advantages of both collagen and A-PRF membranes. Response surface methodology (RSM) was used to design the experimental condition and to correlate the effects of parameters, including chitosan/collagen (chit/col) weight ratio and A-PRF concentration on Young's modulus, mesenchymal stem cell (MSCs) viability and degradation rate of the membranes. Results showed that Young's modulus of the membranes was intensified by increasing chit/col weight ratio and decreasing A-PRF concentration from 3 to 8 MPa. Cell viability of MSCs was improved by both... 

Background: Study of nanostructure-protein interaction for development of various types of nano-devices is very essential. Among carbon nanostructures, carbon nanotube (CNT) provides a suitable platform for functionalization by proteins. Previous studies have confirmed that the CNT induces changes in the protein structure. Methods: Molecular dynamics (MD) simulation study was employed to illustrate the changes occurring in the protein G (PGB) in the presence of a CNT. In order to predict the PGB surface patches for the CNT, Autodock tools were utilized. Results: Docking results indicate the presence of two different surface patches with diverse amino acids: the dominant polar residues in the... 

Sufficient quantity of trace metals is essential for a well performing anaerobic digestion (AD) process. Among the essential trace elements in active sites of multiple important enzymes for AD are iron and nickel ions. In the present study, iron and nickel in the form of Fe2O3 and NiO were coated on TiO2 nanoparticles to be used in batch and continuous operation mode. The effect of TiO2, Fe2O3–TiO2, and NiO–TiO2 nanoparticles on each step of AD process was assessed utilizing simple substrates (i.e. cellulose, glucose, acetic acid, and mixture of H2–CO2) as well as complex ones (i.e. municipal biopulp). The hydrolysis rate of cellulose substrate increased with higher dosages of the coated... 

There are limitations in current medications of articular cartilage injuries. Although injectable bioactive hydrogels are promising options, they have decreased biomechanical performance. Researchers should consider many factors when providing solutions to overcome these challenges. In this study, we created an injectable composite hydrogel from chitosan and human acellular cartilage extracellular matrix (ECM) particles. In order to enhance its mechanical properties, we reinforced this hydrogel with microporous microspheres composed of the same materials as the structural building blocks of the scaffold. Articular cartilage from human donors was decellularized by a combination of physical,... 

Background: A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. Results: This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1–4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and...