Sharif Digital Repository

Objective(s): The molecular basis of “metabolically healthy obese” and “metabolically unhealthy non-obese” phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals. Materials and Methods: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment... 

Background: Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on... 

Crohn's disease and celiac disease belong to a group of autoimmune conditions that affect the digestive system, specifically the small intestine. They both attack the digestive tract and share many symptoms. Thus, the discovery of proper methods would be a major step toward differentiating celiac disease from Crohn's disease. The aim of this study was to search for the metabolic biomarkers to differentiate between these two diseases. Proton nuclear magnetic resonance spectroscopy (1H NMR) was employed as the metabolic profiling method to look for serum metabolites that differentiate between celiac disease and Crohn's disease. Classification of celiac disease and Crohn's disease was done... 

Miniaturized culture systems of hepatic cells are emerging as a strong tool facilitating studies related to liver diseases and drug discovery. However, the experimental optimization of various parameters involved in the operation of these systems is time-consuming and expensive. Hence, developing numerical tools predicting the function of such systems can significantly reduce the associated cost. In this paper, a perfusion-based three dimensional (3D) bioreactor comprising encapsulated human liver hepatocellular carcinoma (HepG2) spheroids are analyzed. The flow and mass transfer equations for oxygen as well as different metabolites such as albumin, glucose, glutamine, ammonia, and urea were... 

BACKGROUND: StrongestPath is a Cytoscape 3 application that enables the analysis of interactions between two proteins or groups of proteins in a collection of protein-protein interaction (PPI) network or signaling network databases. When there are different levels of confidence over the interactions, the application is able to process them and identify the cascade of interactions with the highest total confidence score. Given a set of proteins, StrongestPath can extract a set of possible interactions between the input proteins, and expand the network by adding new proteins that have the most interactions with highest total confidence to the current network of proteins. The application can... 

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... 

Purpose: A basketball match is characterized by intermittent high-intensity activities, thereby relying extensively on both aerobic and anaerobic metabolic pathways. Here, we aimed to compare the metabolic fluctuations between the four 10-min quarters of high-level basketball games using metabolomics analyses. Methods: 70 male basketball players with at least 3 years of experience in the Iran national top-league participated. Before and after each quarter, saliva samples were taken for subsequent untargeted metabolomics analyses, where Principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA) were employed for statistical analysis. Results: Quarters 1 and 3... 

Sulfur mustard (SM) is a vesication chemical warfare agent for which there is currently no antidote. Despite years of research, there is no common consensus about the pathophysiological basis of chronic pulmonary disease caused by this chemical warfare agent. In this study, we combined chemometric techniques with nuclear magnetic resonance (NMR) spectroscopy to explore the metabolic profile of sera from SM-exposed patients. A total of 29 serum samples obtained from 17 SM-injured patients, and 12 healthy controls were analyzed by Random Forest. Increased concentrations of seven amino acids, glycerol, dimethylamine, ketone bodies, lactate, acetate, citrulline and creatine together with the... 

Objective(s): Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Materials and Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify... 

Copper(II) efficiently catalyzes the aerobic oxidation of aryl thioacetamides into the corresponding α-keto aryl thioamides in moderate to high yields in the presence of K2CO3 under O 2 atmosphere. This protocol is simple, clean, and generates water as the only byproduct. A mechanism is proposed for the reaction course. © Georg Thieme Verlag Stuttgart  

The search for efficient chemotherapy drugs and other anti-cancer treatments would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME and in vitro models often do not include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we present a new fully-coupled, agent-based, multi-scale mathematical model of tumor growth, angiogenesis and metabolism that includes important aspects of the TME spanning subcellular-, cellular- and tissue-level scales. The mathematical model is... 

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... 

Concentration-dependent cyto and genotoxicities of graphene oxide (GO) and reduced GO (rGO) sheets on spermatozoa were studied. rGO sheets with various surface chemical states were achieved using hydrazine (N2H 4) hydrothermal (HT) reactions and green tea polyphenols (GTPs). Although 0.1 μg mL-1 graphene could not change sperm viability and kinetic parameters, <40% and 20% of spermatozoa were viable and progressively motile, after 2 h incubation with 400 μg mL-1 GO or rGO, respectively. All the graphene nanomaterials induced concentration- dependent reductions of adenosine triphosphate and NAD+/NADH produced by spermatozoa for motility and metabolic activity. While GO, N 2H4-rGO, and HT-rGO... 

Motivation: The interactions among proteins and the resulting networks of such interactions have a central role in cell biology. Aligning these networks gives us important information, such as conserved complexes and evolutionary relationships. Although there have been several publications on the global alignment of protein networks; however, none of proposed methods are able to produce a highly conserved and meaningful alignment. Moreover, time complexity of current algorithms makes them impossible to use for multiple alignment of several large networks together.Results: We present a novel algorithm for the global alignment of protein-protein interaction networks. It uses a greedy method,... 

Ammonia detoxification is one of the main functions of the liver results in production of urea. In this study ammonia elimination and urea production was simulated in a microchannel mimicking the hepatic porto central axis. Navier- Stockes equations along with convection equations were solved for the related species in the entire domain. Since the Reynolds number was small (~1) the fluid flow regime was laminar. Urea cycle was modeled regarding its four main enzymes. Twelve rate equations were also solved in order to obtain the concentration of each metabolites participating in urea cycle. Concentration of the urea reached its maximum ca. 1.2e-5 M at the end of the channel which is in good... 

Being the second cause of mortality across the globe, there is now a persistent effort to establish new cancer medication and therapies. Any accomplishment in treating cancers entails the existence of accurate identification systems empowering the early diagnosis. Recent studies indicate CTCs’ potential in cancer prognosis as well as therapy monitoring. The chief shortcoming with CTCs is that they are exceedingly rare cells in their clinically relevant concentration. Here, we simulated a microfluidic construct devised for immunomagnetic separation of the particles of interest from the background cells. This separation unit is integrated with a mixer subunit. The mixer is envisioned for... 

Purpose: A basketball match is characterized by intermittent high-intensity activities, thereby relying extensively on both aerobic and anaerobic metabolic pathways. Here, we aimed to compare the metabolic fluctuations between the four 10-min quarters of high-level basketball games using metabolomics analyses. Methods: 70 male basketball players with at least 3 years of experience in the Iran national top-league participated. Before and after each quarter, saliva samples were taken for subsequent untargeted metabolomics analyses, where Principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA) were employed for statistical analysis. Results: Quarters 1 and 3...