Risk factors for cancer

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Risk factors for cancer

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‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎9:20:00 πμ

Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue

‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎9:20:03 πμ

Gene electrotransfer into the skin is of particular interest for the development of medical applications including DNA vaccination, cancer treatment, wound healing or treatment of local skin disorders. However, such clinical applications are currently limited due to poor understanding of the mechanisms governing DNA electrotransfer within human tissue. Nowadays, most studies are carried out in rodent models but rodent skin varies from human skin in terms of cell composition and architecture. We used a tissue-engineering approach to study gene electrotransfer mechanisms in a human tissue context. Primary human dermal fibroblasts were cultured according to the self-assembly method to produce 3D reconstructed human dermal tissue. In this study, we showed that cells of the reconstructed cutaneous tissue were efficiently electropermeabilized by applying millisecond electric pulses, without affecting their viability. A reporter gene was successfully electrotransferred into this human tissue and gene expression was detected for up to 48h. Interestingly, the transfected cells were solely located on the upper surface of the tissue, where they were in close contact with plasmid DNA solution. Furthermore, we report evidences that electrotransfection success depends on plasmid mobility within tissue- rich in collagens, but not on cell proliferation status. In conclusion, in addition to proposing a reliable alternative to animal experiments, tissue engineering produces valid biological tool for the in vitro study of gene electrotransfer mechanisms in human tissue.

Predicting Human Enzyme Family Classes by Using Pseudo Amino Acid Composition

‎Παρασκευή, ‎15 ‎Ιουλίου ‎2016, ‏‎9:20:03 πμ

Background: Enzymes are biological macromolecules which can act as catalysts and help complex biochemical reactions. They can increase the rate of a reaction by reducing its activation energy. Different enzymes can catalyze different chemical reactions. </p><p> Objective: With the appearance of vast human protein data, correctly identifying the human enzymes class is extremely important to understand their functions. However, no computational method was developed to predict enzyme functional classes in human. We aimed to develop a computational method to discriminate human enzymes from non-enzymes and further predict the classes of human enzymes. </p><p> Method: In this paper, the pseudo amino acid composition was proposed to formulate proteins by incorporating rigidity, flexibility and irreplaceability of amino acids. The feature selection technique was used to optimize the feature set. We proposed SVM to perform prediction. </p><p> Results: The results of five-fold cross-validation test show that the overall accuracies are 72.6% and 46.1%, respectively for discriminating human enzymes from non-enzymes and predicting six classes of human enzymes. </p><p> Conclusion: The work in this study provides an efficient method on this issue. Especially, three kinds of new characteristics were introduced to incorporate into PseAAC. The results indicate that the three characteristics of amino acids can be used in human enzyme prediction. </p><p>

Development of a Simple and Accurate RP-HPLC-UV for Determination of Choleretic Drug Alibendol in Human Plasma and Its Application for a Pharmacokinetic Study

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎9:05:03 πμ

An accurate and selective high-performance liquid chromatography with ultraviolet detector (HPLC-UV) method was developed for quantification of alibendol in human plasma. The sample was prepared by one-step liquid-liquid extraction (LLE) using ethyl acetate from plasma. The chromatographic retention times of alibendol and carvedilol (the internal standard; IS) were 4.3 and 3.5 min, respectively, on a reverse phase C₁₈ CAPCELL PAK (250 mm 4.6 mm I.D., 5 μm) column. The isocratic mobile phase consisted of acetonitrile-10 mM sodium phosphate (45:55, v/v; adjusted to pH 3.0 with phosphoric acid). The lower limit of quantitation (LLOQ) was 0.3 μg/mL and no interferences were detected in chromatograms. The developed HPLC method was validated by evaluating its inter- and intra-day precisions and accuracies for a linear concentration range of 0.3 and 20.0 μg/mL. Stability testing showed that alibendol was stable in human plasma during sample processing and storage. The proposed method was successfully applied to the pharmacokinetic study of the single-dose oral administration of 100 mg alibendol tablet in healthy Korean male volunteers. The C_max, T_1/2 and AUC_0-t of alibendol were 5.82 ± 1.40 μg/mL, 1.47 ± 0.43 h, 10.62 ± 2.40 μg·h/mL, respectively.

The Effects of Statin Therapy on the Human Airway

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎9:05:03 πμ

Background: Statins have been long known for their lipid-lowering properties however there has been recent interest in their potential to positively influence clinical outcomes in pulmonary disease processes manifesting primarily as airway disorders. </p><p> Objectives: We review the potential use of statin therapy in respiratory medicine, with particular emphasis on airway disease. We also explore the possible mechanisms for the observed benefits of statins in conditions of the airway. </p><p> Method: A literary review of published articles related to defining the potential scientific basis for touted clinical efficacy, pertinent clinical data and review articles of statin therapy in airway disease. </p><p> Results: There was a vast quantity of publications available pertaining to the topic of interest. </p><p> Conclusion: Statins may have beneficial pleiotropic effects in addition to their actions as potent lipid-lowering agents particularly in patients with chronic obstructive pulmonary disease and post lung transplantation. Further human studies are required to substantiate their possible potential as many of the clinical trials performed to date have not demonstrated the translation of results of these promising scientific and observational studies into positive outcomes in well-designed, randomized, placebo-controlled human trials.

Discrimination of Active and Weakly Active Human BACE1 Inhibitors Using Self-Organizing Map and Support Vector Machine

‎Πέμπτη, ‎14 ‎Ιουλίου ‎2016, ‏‎9:05:03 πμ

&#946;-secretase (BACE1) is an aspartyl protease, which is considered as a novel vital target in Alzheimer&#039;s disease therapy. We collected a data set of 294 BACE1 inhibitors, and built six classification models to discriminate active and weakly active inhibitors using Kohonen’s Self-Organizing Map (SOM) method and Support Vector Machine (SVM) method. Each molecular descriptor was calculated using the program ADRIANA.Code. We adopted two different methods: random method and Self-Organizing Map method, for training/test set split. The descriptors were selected by F-score and stepwise linear regression analysis. The best SVM model Model2C has a good prediction performance on test set with prediction accuracy, sensitivity (SE), specificity (SP) and Matthews correlation coefficient (MCC) of 89.02%, 90%, 88%, 0.78, respectively. Model 1A is the best SOM model, whose accuracy and MCC of the test set were 94.57% and 0.98, respectively. The lone pair electronegativity and polarizability related descriptors importantly contributed to bioactivity of BACE1 inhibitor. The Extended-Connectivity Finger-Prints_4 (ECFP_4) analysis found some vitally key substructural features, which could be helpful for further drug design research. The SOM and SVM models built in this study can be obtained from the authors by email or other contacts.

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