Plasma GBP2 promoter methylation is associated with advanced stages in breast cancer

Blood methylated cell-free DNA (cfDNA) as a minimally invasive cancer biomarker has great importance in cancer management. Guanylate binding protein 2 (GBP2) has been considered as a possible controlling factor in tumor development. GBP2 gene expression and its promoter methylation status in both plasma cfDNA and tumor tissues of ductal carcinoma breast cancer patients were analyzed using SYBR green comparative Real-Time RT-PCR and, Methyl-specific PCR techniques, respectively in order to find a possible cancer-related marker. The results revealed that GBP2 gene expression and promoter methylation were inversely associated. GBP2 was down-regulated in tumors with emphasis on triple negative status, nodal involvement and higher cancer stages (p<0.0001). GBP2 promoter methylation on both cfDNA and tumor tissues were positively correlated and was detected in about 88% of breast cancer patients mostly in (Lymph node positive) LN+ and higher stages. Data provided shreds of evidence that GBP2 promoter methylation in circulating DNA may be considered as a possible effective non-invasive molecular marker in poor prognostic breast cancer patients with the evidence of its relation to disease stage and lymph node metastasis. However further studies need to evaluate the involvement of GBP2 promoter methylation in progression-free survival or overall survival of the patients.     

Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran

International Journal of Peptide Research and Therapeutics - Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and...     

The beneficial role of SIRT1 activator on chemo- and radiosensitization of breast cancer cells in response to IL-6

Molecular Biology Reports - Tumor environmental cytokines, such as IL-6, has a major role in the outcome of radiation and chemotherapy. In this study, we hypothesized that IL-6 mediates its effects...     

Dimerization of Aβ40 inside dipalmitoylphosphatidylcholine bilayer and its effect on bilayer integrity: Atomistic simulation at three temperatures

Amyloid-beta (Aβ) protein is related to Alzheimer disease (AD), and various experiments have shown that oligomers as small as dimers are cytotoxic. Recent studies have concluded that interactions of Aβ with neuronal cell membranes lead to disruption of membrane integrity and toxicity and they play a key role in the development of AD. Molecular dynamics (MD) simulations have been used to investigate Aβ in aqueous solution and membranes. We have previously studied monomeric Aβ40 embedded in dipalmitoylphosphatidylcholine (DPPC) membrane using MD simulations. Here, we explore interactions of two Aβ40 peptides in DPPC bilayer and its consequences on dimer distribution in a lipid bilayer and on the secondary structure of the peptides. We explored that N-terminals played an important role in dimeric Aβ peptide aggregations and Aβ-bilayer interactions, while C-terminals bound peptides to bilayer like anchors. We did not observe exiting of peptides in our simulations although we observed insertion of peptides into the core of bilayer in some of our simulations. So it seems that the presence of Aβ on membrane surface increases its aggregation rate, and as diffusion occurs in two dimensions, it can increase the probability of interpeptide interactions. We found that dimeric Aβ, like monomeric one, had the ability to cause structural destabilization of DPPC membrane, which in turn might ultimately lead to cell death in an in vivo system. This information could have important implications for understanding the affinity of Aβ oligomers (here dimer) for membranes and the mechanism of Aβ oligomer toxicity in AD.     

Biochemical characterization and structural analysis of trypsin from Plodia interpunctella midgut: implication of determinants in extremely alkaline pH activity profile

In the present study, trypsin from Plodia interpunctella (Hübner) is characterized to discover sequence, biochemical and structural features. This enzyme is purified by ion exchange chromatography using fast protein liquid chromatography on proteins from fifth‐instar larvae. The enzyme is optimally active at 50 °C and pH 11.0. The kinetic parameters (K_m and V_max) of the enzyme are 5.3 ± 0.6 µm and 31 ± 1.3 nmol min^?1 mg^?1, respectively (using Nα‐benzoyl‐l ‐arginine ρ‐nitroanilide hydrochloride as substrate). The enzyme is inhibited by the addition of Cu²⁺ and Mn²⁺, whereas it is activated by Li⁺ at high concentrations. Moreover, the enzyme is almost completely inhibited in the presence of Nα‐tosyl‐l ‐lysine chloromethyl ketone hydrochloride and phenylmethanesulphonyl fluoride. To understand some characteristics of P. interpunctella trypsin, including active site structure and alkaline pH profile, a reliable structural model of P. interpunctella trypsin is built based on the Fusarium oxisporum (Schlecht) trypsin cystal structure (Protein Data Bank code: 1GDU). The secondary structure content of the purified trypsin from near‐ultraviolet circular dichroism data shows considerable similarities with that of P. interpunctella trypsin predicted structure. Analysis of pK_a values of active site residues, a type of amino acid residue in the active site cleft and the surface charges of the model and Tribolium castaneum (Herbst) trypsin structure as an insect species from different orders reveals some differences between them. These differences might effect on the microenvironment of the active site cleft and consequently shift its pH profile. The application of multiple theoretical and experimental techniques is well adapted to predict the enzyme structure with high accuracy and this could help in the design of a powerful inhibitor for trypsin with ideal properties.     

Tissue engineering strategies for the induction of angiogenesis using biomaterials

Angiogenesis is touted as a fundamental procedure in the regeneration and restoration of different tissues. The induction of de novo blood vessels seems to be vital to yield a successful cell transplantation rate loaded on various scaffolds. Scaffolds are natural or artificial substances that are considered as one of the means for delivering, aligning, maintaining cell connection in a favor of angiogenesis. In addition to the potential role of distinct scaffold type on vascularization, the application of some strategies such as genetic manipulation, and conjugation of pro-angiogenic factors could intensify angiogenesis potential. In the current review, we focused on the status of numerous scaffolds applicable in the field of vascular biology. Also, different strategies and priming approaches useful for the induction of pro-angiogenic signaling pathways were highlighted.     

Fiber-reinforced computational model of the aortic root incorporating thoracic aorta and coronary structures

Cardiovascular diseases are still the leading causes of death in the developed world. The decline in the mortality associated with circulatory system diseases is accredited to development of new diagnostic and prognostic tools. It is well known that there is an inter relationship between the aortic valve impairment and pathologies of the aorta and coronary vessels. However, due to the limitations of the current tools, the possible link is not fully elucidated. Following our previous model of the aortic root including the coronaries, in this study, we have further developed the global aspect of the model by incorporating the anatomical structure of the thoracic aorta. This model is different from all the previous studies in the sense that inclusion of the coronary structures and thoracic aorta into the natural aortic valve introduces the notion of globality into the model enabling us to explore the possible link between the regional pathologies. The developed model was first validated using the available data in the literature under physiological conditions. Then, to provide a support for the possible association between the localized cardiovascular pathologies and global variations in hemodynamic conditions, we simulated the model for two pathological conditions including moderate and severe aortic valve stenoses. The findings revealed that malformations of the aortic valve are associated with development of low wall shear stress regions and helical blood flow in thoracic aorta that are considered major contributors to aortic pathologies.     

Regulatory networks upon neurogenesis induction in PC12 cell line by small molecules

Alteration in the normal regulatory pathway of differentiation can lead to the induction of programmed cell death. Accordingly, some chemicals like staurosporine, nerve growth factor, pituitary adenylate cyclase activating peptide, and trimethyltin are shown to be able to induce differentiation in vitro, via different mechanisms in the PC12 cell line. Hence, understanding the details of the molecular mechanisms of differentiation induction by these small molecules are important for further application of these molecules in neurogenesis. Therefore, we sought to determine these signaling pathways, using gene regulatory networks analysis. Then, we have conducted a comparative analysis of the alterations in the gene expression pattern of the PC12 cell lines in response to these chemicals at the early stages. Based on the comparative analysis and previous knowledge, we have proposed the affected pathways during differentiation and apoptosis. Our findings could be useful in the development of protocols to reprogramming of neurons by such small molecules with high efficiency.