Breast cancer vaccination comes to age: impacts of bioinformatics

Introduction: Breast cancer, as one of the major causes of cancer death among women, is the central focus of this study. The recent advances in the development and application of computational tools and bioinformatics in the field of immunotherapy of malignancies such as breast cancer have emerged the new dominion of immunoinformatics, and therefore, next generation of immunomedicines. Methods: Having reviewed the most recent works on the applications of computational tools, we provide comprehensive insights into the breast cancer incidence and its leading causes as well as immunotherapy approaches and the future trends. Furthermore, we discuss the impacts of bioinformatics on different stages of vaccine design for the breast cancer, which can be used to produce much more efficient vaccines through a rationalized time- and cost-effective in silico approaches prior to conducting costly experiments. Results: The tools can be significantly used for designing the immune system-modulating drugs and vaccines based on in silico approaches prior to in vitro and in vivo experimental evaluations. Application of immunoinformatics in the cancer immunotherapy has shown its success in the pre-clinical models. This success returns back to the impacts of several powerful computational approaches developed during the last decade. Conclusion: Despite the invention of a number of vaccines for the cancer immunotherapy, more computational and clinical trials are required to design much more efficient vaccines against various malignancies, including breast cancer

Molecular phylogeny and structure prediction of rice RFT1 protein

Rice is one of the most important species in the family of Poaceae. As one of the major crop that is consumed by world population, it is cultivated commercially in many parts of the world. Hence, the phylogeny study of this crop is crucial as a step for improvement of its breeding programs. Phylogenetic relationship among 12 rice cultivars that originated from two common sub-species; Indica and Japonica were inferred by comparing protein sequence data sets derived from its flowering time gene, namely RFT1 and analyzed using maximum parsimony (MP) method. The predicted structure of RFT1 protein was generated by I-TASSER server and analyzed using YASARA software. The result showed that the cultivars were classified into two major groups, where the first group (Japonica) evolved first followed by the second group (Indica). The findings suggested that some cultivars had a close relationship with each other even it is originates from different varieties. The relationships among these cultivars provide useful information for better understanding of molecular evolution process and designing good breeding program in order to generate new cultivar

Preparation of immunotoxin herceptin-botulinum and killing effects on two breast cancer cell lines

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20 beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor

Structural prediction of a novel laminarinase from the psychrophilic glaciozyma antarctica PI12 and its temperature adaptation analysis

Here, we present a novel psychrophilic ß-glucanase from Glaciozyma antarctica PI12 yeast that has been structurally modeled and analyzed in detail. To our knowledge, this is the first attempt to model a psychrophilic laminarinase from yeast. Because of the low sequence identity (<40 %), a threading method was applied to predict a 3D structure of the enzyme using the MODELLER9v12 program. The results of a comparative study using other mesophilic, thermophilic, and hyperthermophilic laminarinases indicated several amino acid substitutions on the surface of psychrophilic laminarinase that totally increased the flexibility of its structure for efficient catalytic reactions at low temperatures. Whereas several structural factors in the overall structure can explain the weak thermal stability, this research suggests that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through existence of longer loops and shorter or broken helices and strands, an increase in the number of aromatic and hydrophobic residues, a reduction in the number of hydrogen bonds and salt bridges, a higher total solvent accessible surface area, and an increase in the exposure of the hydrophobic side chains to the solvent. The results of comparative molecular dynamics simulation and principal component analysis confirmed the above strategies adopted by psychrophilic laminarinase to increase its catalytic efficiency and structural flexibility to be active at cold temperature

Pharmacy Students' Self-Identified Interests in a Hospital Pharmacy Internship Course in Iran

Introduction: After revision of pharmacy curriculum by, Iranian Health and Education Ministry reviewed in 2005, it was decided that pharmacy students need extra internship courses such as hospital internship course. Hospital internship course could provide students with the opportunity to acquire the knowledge and master the skills required for current pharmacy practices in community and hospital setting. The aim of this study was to identify and analyze pharmacy students’ experiences during hospital internship. Methods: Each student attended in 3 wards and provided a logbook for each ward. Students were asked to document at least one topic interesting for them on each day. The collected information was divided into sections and analyzed using SPSS ver 14. Results: Seventeen students enrolled in the course. Endocrinology and nephrology wards had the highest and neurology the lowest number of attended students. Seven hundred and one reported learning subjects were divided into 24 areas. The highest numbers of reported topics were the drugs indications, adverse drug reactions and diagnosis of diseases while the lowest number was pretreatment laboratory tests, pharmacoeconomy, counseling medical staffs and off label use of medications. Gastroenterology and endocrinology wards with 210 reports had the highest and neurology ward with 12 had the lowest number of reports. Conclusion: Completing the logbooks was an encouragement for students to seek and document and learn new topics and also a major feature of the clinical assessment scheme of the course. The majority of the reported topics were learning objectives but not the interventional ones. The present study showed us some areas of pharmacy education which need further attention

The Effect of Sagittal STIR and FLAIR Sequences Compared to Sagittal T2-W for Characterizing MS Lesions in Cervical Spine MRI

Purpose: Multiple Sclerosis (MS) is an acute, autoimmune, and inflammatory disease in the central nervous system. This study investigated the effect of sagittal Short Tau Inversion Recovery (STIR) and T2-W Fluid Attenuated Inversion Recovery (FLAIR) sequences rather than sagittal T2-W as complementary sequences in patients with cervical spinal cord lesions and suspected MS. Materials and Methods: This cross-sectional study was performed on all individuals referred to the Shahid Ghazi MRI center in Sanandaj for six months. Sixty patients with a cervical spine MRI request that were suspected of having MS were examined. The number of MS plaques in the sagittal T2-W FSE, sagittal STIR, and sagittal T2-W FLAIR were recorded separately. A comparison between routine sequences and sequence supplementation has been made for characterizing MS plaque in the spine. Results: Results showed that the greatest agreement was related to sagittal STIR, and sagittal FLAIR (Cohen’s kappa = 0.56). Whereas the least agreement values were from sagittal T2-W and sagittal FLAIR, STIR and FLAIR, T2-W and FLAIR, T2-W and STIR (Cohen’s kappa = 0.20, 0.33, 0.48, 0.55), respectively. Sagittal STIR and sagittal FLAIR were excellent predictors for MS plaques diagnosis due to the area under the ROC curve = 0.56; sensitivity (95% CI) = [0.85 (0.73426 to 0.929044)] and specificity (95% CI) = [0.46 (0.336699 to 0.600035)]. Conclusion: Results show that FLAIR T2-W images in sagittal sequence are appropriate for detecting lesions around spinal cord lesions. Furthermore, using thresholds obtained via statistical analysis, plaques in the cervical spinal cord can be identified in sagittal STIR images

TS-AMIR: a topology string alignment method for intensive rapid protein structure comparison

<p>Abstract</p> <p>Background</p> <p>In structural biology, similarity analysis of protein structure is a crucial step in studying the relationship between proteins. Despite the considerable number of techniques that have been explored within the past two decades, the development of new alternative methods is still an active research area due to the need for high performance tools.</p> <p>Results</p> <p>In this paper, we present TS-AMIR, a Topology String Alignment Method for Intensive Rapid comparison of protein structures. The proposed method works in two stages: In the first stage, the method generates a topology string based on the geometric details of secondary structure elements, and then, utilizes an n-gram modelling technique over entropy concept to capture similarities in these strings. This initial correspondence map between secondary structure elements is submitted to the second stage in order to obtain the alignment at the residue level. Applying the Kabsch method, a heuristic step-by-step algorithm is adopted in the second stage to align the residues, resulting in an optimal rotation matrix and minimized RMSD. The performance of the method was assessed in different information retrieval tests and the results were compared with those of CE and TM-align, representing two geometrical tools, and YAKUSA, 3D-BLAST and SARST as three representatives of linear encoding schemes. It is shown that the method obtains a high running speed similar to that of the linear encoding schemes. In addition, the method runs about 800 and 7200 times faster than TM-align and CE respectively, while maintaining a competitive accuracy with TM-align and CE.</p> <p>Conclusions</p> <p>The experimental results demonstrate that linear encoding techniques are capable of reaching the same high degree of accuracy as that achieved by geometrical methods, while generally running hundreds of times faster than conventional programs.</p

Cold adaptations study of glycosyl hydrolase enzymes via computational methods

Psychrophiles are cold loving organisms that have adapted to live in permanently cold environments. These microorganisms synthesize psychrophilic enzymes with high catalytic efficiencies at cold temperaturesranging from -20°C to +10°C. This research intends to perform an in silico analysis of the cold adaptation of Glycosyl hydrolase enzymes isolated from psychrophilic yeast Glaciozyma antarctica. Two enzyme were selected; ß-mannanase (PMAN) and ß-glucanase (PLAM) from two different glycosyl hydrolase families with different domains. A 3D model was predicted for both genes using a fold recognition method. The proteins were comparatively studied against their mesophilic, thermophilic, and hyperthermophilic counterparts. The study of these enzymes illustrates that they mostly use similar strategies for cold adaptation.The structure of PLAM and PMAN consist of longer loops in three different positions. Their structure also has several amino acids substitution including increased number of alanine, glycine, and polar residues and decreased number of proline, arginine, and hydrophobic residues. The PLAM and PMAN structure showed longer motions around the entrance region to active site. A lower number of salt bridges and H-bonds have been observed in the PLAM and PMAN structure. PLAM consists of 5 salt bridges while its homologous proteins have 9, 7, and 18 salt bridges, respectively. Also, the number of H-bonds per residue is 0.54 where it is 0.62, 0.63, and 0.70 for its homologous counterparts. Furthermore, PMAN includes 5 salt bridges in its structure while its homologous counterparts have 10, 14, and 21 salt bridges, respectively. The number of H-bonds per residue for PMAN is 0.62 while it is 0.71, 0.73 and 0.78 for its homologous counterparts. The PLAM structure has 41% of secondary structure, while its homologous counterparts have 54%, 58%, and 60% of secondary structure. Also, this percentage is 47% for PMAN, and 48%, 50%, and 53% for its homologous proteins. Additionally, they also use different strategies related to the role of salt bridges in their structure. The PLAM structure contains alternative salt bridges connecting inner and outer leaflets, while the PMAN structure includes weakly linked salt bridges between residues located on a loop instead of ß-sheet. In conclusion, in silico analysis of two psychrophilic proteins revealed novel characteristics of these cold adapted enzymes. The analysis showed the adopted strategies by these two proteins in contributing to the general and local flexibility of their structure and increase capability of the enzymes to be active at cold temperatures. The presented findings in this research will assist future attempts in the rational design of enzymes with enhanced enzymatic capabilities

PREVALENCE OF HYPERTENSION IN WORKERS OF VEGETABLE OIL REFINERIES IN TEHRAN

968 male workers employed in five vegetable oil refineries were studied to discover the effects of age, length of employment and smoking habit on the prevalence of hypertension. The results obtained indicate that the overall prevalence of hypertension is 6.61% showing a direct relationship to the age. Considering the length of employment only, in the workers aged 50 and above, there is also a direct relation between the length of employment and prevalence of hypertension. Furthermore, the results show that not only smoking causes elevation of blood pressure, but the number of cigarettes smoked per day is also important, i.e. the workers who smoke more have a higher prevalence of abnormal pressure