Prediction of protein-protein interactions using protein signature profiling

Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain interactions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as "interacting". In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area under the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs increased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on average 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.     

Evaluation of the binding effect and cytotoxicity assay of 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione on calf thymus DNA: spectroscopic,calorimetric, and molecular dynamics approaches

With advances in new drug therapies, it is essential to understand the interactions between drugs and target molecules. In this study, we applied multiple spectroscopic techniques including absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, calorimetric, and molecular dynamics (MD) simulation to study the interaction between 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione (PPF) and calf thymus DNA (ct DNA) in the absence or presence of histone H1. PPF exhibits a high binding affinity towards ct DNA in binary and ternary systems. In addition, the result for the binding constant was observed within the range 10⁴ M⁻¹ achieved through fluorescence quenching data, while the values for enthalpy and entropy changes for ct DNA–PPF and (ct DNA–H1) PPF complexes were measured to be −72.54 kJ.mol⁻¹, −161.14 J.mol⁻¹ K⁻¹, −85.34 kJ.mol⁻¹, and −19.023 J.mol⁻¹ K⁻¹, respectively. Furthermore, in accordance with circular dichroism spectra, the inducement of ct DNA structural changes was observed during binding of PPF and H1 in binary and ternary system forms. The essential roles of hydrogen bonding and van der Waals forces throughout the interaction were suggested using thermodynamic parameters. According to the obtained data, the interaction mode of ct DNA–PPF and (ct DNA–H1) PPF complexes was intercalation binding. Suggested by the MD simulation study, the ct DNA–H1 complex caused a reduction in the stability of the DNA structure in the presence or absence of ligand, which demonstrated that PPF as an intercalating agent can further distort the structure. The information achieved from this study will be very helpful in understanding the effects of PPF on the conformational state of ct DNA in the absence or presence of the H1 molecule, which seems to be quite significant for clarifying the mechanisms of action and its pharmacokinetics.     

Metal Ions Bound to Prion Protein Affect its Interaction with Plasminogen Activation System

The Protein Journal - Prion diseases are a group of neurodegenerative diseases, which can progress rapidly. Previous data have demonstrated that prion protein (PrP) stimulates activation of...     

Heavy metal phytoremediation of aqueous solution by Typha domingensis

Aquatic Ecology - More has yet to be indicated on the ability of microphyte plants for the removal of heavy metals from contaminated environments. In the present research, the ability of the...     

Intraovarian injection of miR-224 as a marker of polycystic ovarian syndrome declines oocyte competency and embryo development

miR-224 is associated with polycystic ovary syndrome (PCOS) that is an epidemic in reproductive age women. Most studies of miR-224 have focused on in vitro analyses, whereas the in vivo effects are not widely understood. In this study, we have conducted in silico analysis and found two potential miR-224 target genes, Ptx3 and Smad4 that have roles in folliculogenesis. Because patients with PCOS have decreased numbers of follicular cells related to cell apoptosis, we also investigated two apoptotic genes, Bax and Bcl2. We used the intraovarian injection method to deliver miR-224 into a mouse model. Histological examination of the ovaries was done by fluorescent microscope. Fertilization, cleavage, and developmental competence rates were counted under a stereomicroscope and compared between the studied groups. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of miR-224 was conducted to determine the levels of the studied genes in the oocytes, cumulus cells, and blastocysts. The numbers of oocytes and fertilization rate indicated a higher apoptosis index ( p < 0.05) and increased numbers of degenerated embryos with irregular blastomeres and fragmented cytoplasm in the experimental group. RT-PCR results indicated a significant increase in miR-224 levels in the manipulated group. Of the four analyzed genes, Ptx3, Smad4, and Bcl2 had decreased levels in the transfected group, with increased Bax expression ( p < 0.05). This data showed that miR-224 negatively affected ovulation in the mouse model by decreasing Ptx3 and Smad4 expressions. The changes in Bcl2 and Bax expression levels, as apoptosis biomarkers, showed that apoptosis was a secondary outcome of the effect of miR-224.     

Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

The cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV-CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC-mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer.     

CTNNBIP1 downregulation is associated with tumor grade and viral infections in gastric adenocarcinoma

Gastric cancer is a life-threatening disease; resulting from interaction among genetic, epigenetic, and environmental factors. Aberrant dysregulation and methylation changes in Wnt/β-catenin signaling downstream elements are a prevalent phenomenon encountered in gastric tumorigenesis. Also, viral infections play a role in gastric cancer development. CTNNBIP1 (β-catenin interacting protein 1) gene is an antagonist of Wnt signaling which binds to the β-catenin molecules. The CTNNBIP1 function as tumor suppressor gene or oncogene in different types of cancer is controversial. Moreover, its function and regulatory mechanisms in gastric cancer progression is unknown. In the present study, we examined CTNNBIP1 gene expression, the methylation status of the regulatory region of the gene, and their association with Epstein–Barr virus (EBV), and cytomegalovirus (CMV) and Helicobacter pylori infections in human gastric adenocarcinoma tissues in comparison with their adjacent nontumoral tissues. Our data revealed a significant downregulation of CTNNBIP1 in gastric tumors. Female patients showed lower level of CTNNBIP1 than males (p < 0.05). Also, decreased expression of CTNNBIP1 was markedly associated with well-differentiated tumor grades (p < 0.05). No methylation change was observed between tumoral and nontumoral tissues. Additionally, CTNNBIP1 down regulation was significantly associated with CMV infection (p < 0.05). In the absence of EBV infection, lower expression of CTNNBIP1 was observed. There was no association between H. pylori infection and CTNNBIP1 expression. Our findings revealed the tumor suppressor role for CTNNBIP1 in gastric adenocarcinoma. Interestingly, EBV and CMV infections modulate CTNNBIP1 expression.     

Adjuvant chemotherapy with melatonin for targeting human cancers: A review

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.