Comparative molecular docking analysis of essential oil constituents as elastase inhibitors

Elastase is a protease or proteolytic enzyme, responsible for the breakdown of protein. There are eight human genes encoding for elastase, of which Elastase-1 (CELA-1) and Elastase-2 (ELANE) has significant implications on human diseases. Elastase-1 is primarily expressed in skin keratinocytes and is regarded as the major cause for the blistering in bullous pemphigoid, which affects the skin. On the other hand, Elastase-2 (ELANE), is expressed in the azurophil granules of neutrophils, is responsible for pulmonary emphysema and cyclic hematopoiesis a rare genetic disorder. Elastase is also produced by bacteria such as Pseudomonas aeruginosa, and forms the virulent factor in human. The ingredients from essential natural oils were found to have wound healing effects on non-healing wounds that is interfered by elastase due to microbial infection. Essential oils such as citral, citronellal, geranial, geraniol, and thymol were screened for their inhibitory activity on elastase produced by neutrophil, skin, and Pseudomonas aeruginosa by docking and were analyzed for their subcutaneous ADMET properties by ADME – TOX – Web server

Influence of photon beam energy on IMRT plan quality for radiotherapy of prostate cancer

BackgroundIntensity-modulated radiation therapy (IMRT) has been widely used for prostate cancer treatments. 6MV photon beams were found to be an effective energy choice for most IMRT cases. The use of high-energy photons raise concerns about increased leakage and secondary neutron dose for the patients.AimIn this work, the effect of beam energy on the quality of IMRT plans for prostate radiotherapy was systematically studied for competing IMRT plans optimized for delivery with either 6 or 10MV beams.Materials and MethodsA cohort of 20 prostate cases was selected for this study. All patients received full-course IMRT treatments to a dose of 79.2Gy to PTV in 44 fractions. For all of the cases we developed treatment plans using 6 MV and 10MV intensity-modulated beams with identical dose volume constraints.ResultsPercentage of doses received by the percentage volume of PTV was higher for 6MV photons compared to 10MV photons for 12 patients, less than or equal to 1% for 6 patients and 2.6%, 3.6% for the remaining 2 patients irrespective of the PTV volume. Percentage doses received by 15% of bladder volume were higher for 10 MV photons. Percentage doses received by 15% of rectum volume were also higher for 10 MV photons.ConclusionsSince there is no greater advantage from 10MV photons as compared with 6MV photons in large volume pelvic IMRT dosimetry and also 10MV photons lie on the threshold energy border for the induction of photo neutrons from the accelerator components, we recommend the use of 6MV photons for IMRT of prostate cancer to achieve better results in tumour control and acceptable probability of complication rate

Binding Mode of CpG Oligodeoxynucleotides to Nanoparticles Regulates Bifurcated Cytokine induction via Toll-like Receptor 9

The interaction of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) with Toll-like receptor 9 (TLR9) activates the immune system. Multimeric class A CpG ODNs induce interferon-α (IFN-α) and, to a lesser extent, interleukin-6. By contrast, monomeric class B CpG ODNs induce interleukin-6 but not IFN-α. This difference suggests that the multimerization of CpG ODN molecules is a key factor in IFN-α induction. We multimerized class B CpG ODN2006x3-PD molecules that consist entirely of a phosphodiester backbone onto quantum dot silicon nanoparticles with various binding modes. Herein, we present the binding mode-dependent bifurcation of cytokine induction and discuss its possible mechanism of CpG ODN and TLR9 interaction. Our discoveries also suggest that nanoparticles play roles in not only delivery of CpG ODNs but also control of CpG ODN activity

Insights into the Binding of 3-(1-Phenylsulfonyl-2-methylindol-3-ylcarbonyl) Propanoic Acid to Bovine Serum Albumin: Spectroscopy and Molecular Modelling Studies

Serum albumin is a globular protein which is most abundant in human that binds remarkably with wide range of drugs. A reliable prediction of protein and drug binding at the atomic level by optical spectroscopy and molecular modeling methods provides the basis for the design of new drug compounds. In the current study, A newly synthesized 3-(1-Phenylsulfonyl-2-methylindol-3- ylcarbonyl) propanoic acid (PA) which has a antifungal and anti bacterial effects also plays vital role for the nutrition, micro biome and physiology triangle. It has been reported that 90% of PA quantity is metabolized by the liver and the rest is transported into the peripheral blood, since PA has binding characteristics, understanding pharmacokinetic mechanism of the drug is important. In this regard, the binding of PA-Bovine Serum Albumin (BSA) was investigated by UV-Vis, fluorescence spectroscopy and molecular docking studies. From the experimental and modeling studies it is observed that PA could bind BSA through the hydrophobic force, and hydrogen bonding. The current study reveals that the optical spectroscopy and molecular modeling techniques could be effectively used to study the design of new drug and understanding their pharmacokinetics