Sharif Digital Repository

Background: A comprehensive intuition of the systemic lupus erythematosus (SLE), as a complex and multifactorial disease, is a biological challenge. Dealing with this challenge needs employing sophisticated bioinformatics algorithms to discover the unknown aspects. This study aimed to underscore key molecular characteristics of SLE pathogenesis, which may serve as effective targets for therapeutic intervention. Methods: In the present study, the human peripheral blood mononuclear cell (PBMC) microarray datasets (n = 6), generated by three platforms, which included SLE patients (n = 220) and healthy control samples (n = 135) were collected. Across each platform, we integrated the datasets by... 

The artificial neural network (ANN) is a sort of machine learning method which has been used in determination of risk of human disorders. In the current investigation, we have created an ANN and trained it based on the genetic data of 401 multiple sclerosis (MS) patients and 390 healthy subjects. Single nucleotide polymorphisms (SNPs) within ANRIL (rs1333045, rs1333048, rs4977574 and rs10757278), EVI5 (rs6680578, rs10735781 and rs11810217), ACE (rs4359 and rs1799752), MALAT1 (rs619586 and rs3200401), GAS5 (rs2067079 and rs6790), H19 (rs2839698 and rs217727), NINJ2 (rs11833579 and rs3809263), GRM7 (rs6782011 and rs779867), VLA4 (rs1143676), CBLB (rs12487066) and VEGFA (rs3025039 and... 

In this paper, the Extended Kalman filtering (EKF) approach has been used to infer gene regulatory networks using time-series gene expression data. Gene expression values are considered stochastic processes and the gene regulatory network, a dynamical nonlinear stochastic model. Using these values and a modified Kalman filtering approach, the model's parameters and consequently the interactions amongst genes are predicted. In this paper, each gene-gene interaction is modeled using a linear term, a nonlinear one, and a constant term. The linear and nonlinear term coefficients are included in the state vector together with the gene expressions' true values. Through the extended Kalman... 

Ankylosing spondylitis (AS) is a systemic inflammatory disorder of joints and entheses. Recent studies have reported an increased prevalence of dementia in AS patients. However, data for exploring the association between dementia and AS remain uncertain. In this study, enriched pathways and differentially expressed genes (DEGs) were identified in whole blood transcription data of AS patients obtained from the gene expression omnibus (GEO) database; using gene set enrichment analysis (GSEA) and differential expression analysis. Four pathways, including oxidative phosphorylation, Alzheimer's, Parkinson's, and Huntington's diseases were significantly enriched in AS patients compared to the... 

Background: Small scale robotics have attracted growing attention for the prospect of targeting and accessing cell-sized sites, necessary for high precision biomedical applications and drug/gene delivery. The loss of controlled gene therapy, inducing systemic side effects and reduced therapeutic efficiency, can be settled utilizing these intelligent carriers. Methods: Newly proposed solutions for the main challenges of control, power supplying, gene release and final carrier extraction/degradation have shifted these smart miniature robots to the point of being employed for practical applications of transferring oligonucleotides (pDNA, siRNA, mRNA, etc.) in near future. Conclusion: In this... 

Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary... 

Understanding the functionality of proteins has emerged as a critical problem in recent years due to significant roles of these macro-molecules in biological mechanisms. However, in-laboratory techniques for protein function prediction are not as efficient as methods developed and processed for protein sequencing. While more than 70 million protein sequences are available today, only the functionality of around one percent of them are known. These facts have encouraged researchers to develop computational methods to infer protein functionalities from their sequences. Gene Ontology is the most well-known database for protein functions which has a hierarchical structure, where deeper terms are... 

Cationic polymers such as poly-L-lysine (PLL) are able to interact electrostatically with DNA to produce polymeric systems with nanometric diameters due to the neutralization and accumulation of DNA. This study integrates the outstanding properties of carbon quantum dots (CQDs) with PLL to develop a novel gene delivery vehicle with a core-shell hybrid nanostructure. The CQD/PLL core-shell nanoparticles (NPs) were, therefore, synthesized in such a way that they had narrow size distribution and an average diameter under 10 nm, both of which were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) spectroscopy exhibited that... 

Background: Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients. Methods: An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein-protein interaction (PPI) networks. Then, functional clusters in PPI... 

Background: One of the negative effects of cardiac sympathetic hyperactivity is pathologic hypertrophy. Recent studies have indicated that large tumor suppressor (LATS) is one of the molecules which play a critical role in cardiomyocyte apoptosis. Considering the preventive role of exercise training, we evaluated the effects of endurance training on LATS gene expression and its upstream pathway in the present study. Methods: Eighteen male Wistar rats were randomly divided into 2 groups: Endurance and control. Endurance training was performed for 8 weeks, 1 hour per day, and 6 days per week on the treadmill at a 15° inclination. Pathologic hypertrophy was induced with the injection of 3... 

The graphene-based materials with unique, versatile, and tunable properties have brought new opportunities for the leading edge of advanced nanobiotechnology. In this regard, the use of graphene in gene delivery applications is still at early stages. In this study, we successfully designed a new complex of carboxylated-graphene (G-COOH) with ethidium bromide (EtBr) and used it as a nanovector for efficient gene delivery into the AGS cells. G-COOH, with carboxyl functions on its surface, in the presence of EtBr, formaldehyde, and cyclohexylisocyanide were participated in Ugi four component reaction to fabricate a stable amphiphilic graphene-EtBr (AG-EtBr) composite. The coupling reaction was... 

Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external... 

In recent years, analyzing genome-wide expression profiles to find genetic markers has received much attention as a challenging field of research aiming at unveiling biological mechanisms behind complex disorders. The identification of reliable and reproducible markers has lately been achieved by integrating genome-scale functional relationships and transcriptome datasets, and a number of algorithms have been developed to support this strategy. In this paper, we present a promising and easily applicable tool to accomplish this goal, namely CytoGTA, which is a Cytoscape plug-in that relies on an optimistic game theoretic approach (GTA) for identifying subnetwork markers. Given transcriptomic... 

Carbosilane dendrimers are a particular type of dendrimer structure that has been used as delivery vehicles for drugs and nucleic acids. They have a defined structure according to their generation number, and their terminal groups can be rendered cationic or anionic. The cationic charges can address the limitation of electrostatic repulsion between the negatively charged phosphate groups of nucleic acids and negatively charged cell membranes. Specific drugs can be loaded into the central part of the dendrimer or attached at the exterior, and the overall positive charge may improve the efficacy of anti-inflammatory drugs. One promising feature of dendrimers is their non-toxicity both in vitro...