Background and the purpose of the study: Of the gene delivery systems, non-viral polycationic gene delivery nanosystems have been alternatively exploited as a relatively safe delivery reagents compared to viral vectors. However, little is known about the genomic impacts of these delivery systems in target cells/tissues. In this study, the toxicogenomics and genotoxicity potential of some selected polycationic lipid/polymer based nanostructures (i.e., Oligofectamine (OF), starburst polyamidoamine Polyfect (PF) and diaminobutane (DAB) dendrimers) were investigated in human alveolar epithelial A549 cells.ethods: To study the nature and the ontology of the gene expression changes in A549 cells upon treatment with polycationic nanostructures, MTT assay and microarray gene expression profiling methodology were employed. For microarray analysis, cyanine (Cy3/Cy5) labeled cDNA samples from treated and untreated cells were hybridized on target arrays housing 200 genes. Results and major conclusions: The polycationic nanosystems induced significant gene expression changes belonging to different genomic ontologies such as cell defence and apoptosis pathways. These data suggest that polycationic nanosystems can elicit multiple gene expression changes in A549 cells upon their chemical structures and interactions with cellular/sub cellular components. Such impacts may interfere with the main goals of the desired gene medicine.

Studies show that anxiety is one of the most common symptoms of mercury poisoning. The mechanism of mercury toxicity is not known in detail. This study aimed to broaden our understanding of mercury-induced anxiety and suggest potential protective agents. A list of genes associated with anxiety was extracted from the overlap between GeneCards, DisGeNET, and Diseases to decipher protein-protein interaction (PPI) and core sub-network. The comparative toxicogenomic database (CTD) helped to identify core mercury targets in anxiety disorders. Detailed interactions and relevant functions were obtained through GeneMANIA. Network pharmacology and molecular docking approaches identified potential protective agents-mercury target interactions. Among the eight proteins in the anxiety-related core sub-network (IL1B, IL6, TNF, IFNG, STAT3, TP53, EP300, and ESR1), the top-ranked proteins IL1B, IL6, TNF, and IFNG were revealed as core mercury targets with key interactions in disrupting the inflammatory responses and interfering with cellular processes. GeneMANIA highlighted the functions of CASP1, TNFAIP3, and SQSTM1 as first neighbors of the core mercury targets. Quercetin, selenium, curcumin, and glutathione were specified as factors that target the most mercury-responsive genes. Molecular docking revealed strong binding affinities between protective agents (quercetin and curcumin) and core target proteins. This study presented a network biology approach in toxicology and pharmacology to further understand the mechanism of mercury toxicity and its therapeutic solution for anxiety disorders.

Background and purpose: The Internet offers a wide range of online digital resources for the field of Toxicology. Methods: The history of toxicology and electronic data collections are reviewed. This review presents a brief and non-comprehensive overview of a representative sampling of some of the broad array of toxicology-related learning, tutorial and information resources now becoming widely available to educators, health professionals, students and the general public via the Internet. Results: A broad variety of useful learning and reference resources in the general fields of toxicology and the environmental health sciences is provided to introduce the reader to the diverse types of information currently available. Distance education and educational media resources are also available online in the field of toxicology. As molecular biology and computational tools improve, new areas within toxicology such as structural activity relationship analysis, mutational spectra databases and toxicogenomics, now have resources online as well.Conclusion: The sources and Internet links contained in this review will hopefully constitute a useful resource of basic toxicology information that should be readily accessible to most if not all Iranian readers.

Background: Extreme obesity pathology is with a risk factor for heart failure (HF), whereas the obesity paradox in HF shows that obese subjects had a good prognosis. The mechanism underlying the obesity paradox in HF prognosis is unclear till now. We aimed to provide evidence for the molecular mechanisms of the obesity paradox in HF. Methods: Differentially expressed genes (DEGs) in ischemic HF samples were identified in the GSE57338 and GSE5406 datasets. Weighted gene co-expression network analysis (WGCNA) modules and a protein-protein interaction network (PPI) were constructed. HF-associated DEGs and pathways were screened in the Comparative Toxicogenomics Database (CTD). The expression of hub genes in adipose tissues from obese patients and LV samples from HF patients were validated in microarray datasets. Results: Three HF-associated WGCNA modules were identified and DEGs were associated with the ‘hsa04115: p53 signaling pathway’. SERPINE1 was the only common gene between DEGs and HF-associated genes in the CTD database. The SERPINE1 gene was downregulated in the white adipose tissues compared with brown adipose tissues (P = 3.90e-03) and was upregulated in the omental adipose tissues from obese patients compared with lean subjects (P = 3.85e-02). Conclusion: The downregulation of SERPINE1 expression might be responsible for the obesity paradox in HF via interacting with ESR1.

Nanoparticles (NPs) are a heterogeneous group of materials that have various applications, and their risk assessment is an essential condition. This study aimed to review the applicable risk assessment methods in occupational and environmental exposures to NPs. A literature search for articles published since 2005 in Web of Knowledge, Scopus, PubMed, Science Direct, and Google Scholar, using appropriate keywords such as “ Risk Assessment, ” “ Nanoparticle, ” and “ Nanomaterial, ” revealed 56 articles, which were screened by two researchers. A total of 15 articles were reviewed in full text. In total, 11 applied techniques for NP risk assessment were analyzed. Seven methods were quantitative, and four were qualitative. The quantitative methods were Integrated Probabilistic Risk Assessment (IPRA), Integrated Probabilistic Environmental Risk Assessment (IPERA), Quantitative Structure-Activity QSTR-Perturbation Model, Lung Dosimetry Modeling for Quantitative Risk Assessment (LDMQRA), Physiologically Based Pharmacokinetic Modeling (PBPK), Risk assessment based on toxicokinetic modeling, and Risk assessment of NPs with Spray Application. The qualitative methods were Application of Toxicogenomics for Risk Assessment, Luminous Microbial Array for Toxicity Risk Assessment (Lumi MARA), Control Banding Nano Tool (CBNT), and Stoffenmanager Nano Tool. It can be concluded that each of the studied methods evaluates an NP and is specifically used for that NP. A general risk assessment approach cannot be applied to all NPs but should be separately investigated by different processes.

There is a high need to develop a novel toxicity test platform based on embryonic stem cells (ESCs), in particular human ESC (hESCs), to streamline the drug development RandD process and evaluation of drug toxicity in clinical studies, reduce related costs and thus to not only increase the safety of patients but also to reduce the number of animals due to earlier detection of adverse effects. The FP7 framework consortium ESNATS addresses current shortcomings in toxicity testing: It aims to develop a novel testing system taking advantage of the unique potential of hESCs, including their capacity to self-renew, constituting a potentially unlimited source of cells and their pluripotency, providing a source for cells of different phenotypes required for toxicity testing. Furthermore, hESC-derived somatic cells are physiologically relevant for toxicity endpoints, offering a perspective of tests with improved predictivity. To reach the project goals, a battery of toxicity tests has been developed using hESC lines subjected to standardised culture and differentiation protocols. Genomics approaches are used to determine predictive toxicogenomics signatures. The individual tests will be integrated into an “all-in-one” testing strategy. To ensure practical usage in the pharmaceutical industry, concepts for automated ESC culture will be developed and the test systems will be scaled up. The ESNATS project provides valuable information for risk identification in regulatory toxicology. Alternative testing strategies are highly needed in this field of work to limit the number of animal tests required to comply with the REACH. Moreover, human induced pluripotent stem cells (iPS) will provide additional tools to study the pathophysiology of monogenetic diseases enabling more distinctive and informative assay systems.

Objective: This study aimed to identify several potentially key genes associated with the pathogenesis of Takayasu’s arteritis (TA). This identification may lead to a deeper mechanistic understanding of TA etiology and pave the way for potential therapeutic approaches.Materials and Methods: In this experimental study, the microarray dataset GSE33910, which includes expression data for peripheral blood mononuclear cell (PBMC) samples isolated from TA patients and normal volunteers, was downloaded from the publicly accessible Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified in PBMCs of TA patients compared with normal controls. Gene ontology (GO) enrichment analysis of DEGs and analysis of protein-protein interaction (PPI) network were carried out. Several hub proteins were extracted from the PPI network based on node degrees and random walk algorithm. Additionally, transcription factors (TFs) were predicted and the corresponding regulatory network was constructed.Results: A total of 932 DEGs (372 up- and 560 down-regulated genes) were identified in PBMCs from TA patients.Interestingly, up-regulated and down-regulated genes were involved in different GO terms and pathways. A PPI network of proteins encoded by DEGs was constructed and RHOA, FOS, EGR1, and GNB1 were considered to be hub proteins with both higher random walk score and node degree. A total of 13 TFs were predicted to be differentially expressed. A total of 49 DEGs had been reported to be associated with TA in the Comparative Toxicogenomics Database (CTD). The only TA marker gene in the CTD database wasNOS2, confirmed by three studies. However, NOS2 was not significantly altered in the analyzed microarray dataset. Nevertheless, NOS3 was a significantly down-regulated gene and was involved in the platelet activation pathway.Conclusion: RHOA, FOS, and EGR1 are potential candidate genes for the diagnosis and therapy of TA.