A New Hybrid Approach to Optimize the MRR and Tool Wear of EDM for Al/TiC Composites

Electro Discharge Machining (EDM) is extensively used to machine the ceramic composites and electrically conductive materials but due to the abrasive reinforcement, the wear rate may get reduced. This work spotlights on optimizing the developed mathematical models of the Metal Removal Rate (MRR) and Tool Wear Rate (TWR) in terms of machining parameters. The Response Surface Methodology (RSM) (L31 empirical model) was used for conducting the basic trails with Al/TiC composites of various compositions. The mechanical and physical properties of Al/TiC composites were analyzed and the SEMmorphology of the machined samples was examined using FESEM. The models developed for predicting responses were tested by analysis of variance (ANOVA) to evaluate its adequacy. The optimization of machining parameters was done by Genetic Algorithm (GA) to acquire minimum TWR with maximum MRR

Hypoxia Induced ER Stress Response as an Adaptive Mechanism in Cancer

It is evident that regions within tumors are deprived of oxygen, which makes the microenvironment hypoxic. Cancer cells experiencing hypoxia undergo metabolic alterations and cytoprotective adaptive mechanisms to survive such stringent conditions. While such mechanisms provide potential therapeutic targets, the mechanisms by which hypoxia regulates adaptive responsessuch as ER stress response, unfolded protein response (UPR), anti-oxidative responses, and autophagyremain elusive. In this review, we summarize the complex interplay between hypoxia and the ER stress signaling pathways that are activated in the hypoxic microenvironment of the tumors

Studies on Physico-Chemical and Pharmacokinetic Properties of Olanzapine through Nanosuspension

The increasing frequency of poorly water soluble new chemical entities exhibiting therapeutic activity is of major concern to the pharmaceutical industry. Olanzapine is an atypical antipsychotic used orally in treatment of Schizophrenia. Also, it has poor aqueous solubility (BCS Class II drug) whose oral bioavailability has been reported as only 40%. In this study olanzapine nanosuspension was prepared using Solvent diffusion followed by sonication technique. The nanosuspension was characterized for particle size distribution, poly dispersity index, zeta potential, crystallinity study (DSC), invitro dissolution release profile and pharmacokinetic studies. Average size of the nanoparticles in F6 was 122.2nm. Saturation solubility of optimized batch of nanosuspension and the plain drug were found to be 2851.3±6.3 μg/ml and 251.3 ±6.1 μg/ml, respectively. In vitro cumulative release from the nanosuspension was 83.54 % at 45 min when compared to pure drug 22.91 % and freeze dried nanosuspension 92.67%. Pharmacokinetic studies in rats revealed that AUC (0–∞) was increased and clearance was decreased when Olanzapine nanosuspensions were administered orally compared with that of Olanzapine suspension which in turn 2 folds increased bioavailability. The enhanced relative bioavailability by the formulation might be attributed to oral bioavailability can be attributed to the adhesiveness of the drug nanosuspension, increased surface area (due to reduction in particle size), increased saturation solubility, leading to an increased concentration gradient between the gastrointestinal tract lumen and blood, and increased dissolution velocity. This enhancement in bioavailability will lead to a subsequent reduction in drug dose, rendering the therapy cost-effective and obliterating any undue drug dumping in the body.Thus, Nanosuspension seems to be a promising approac

Tricaproin Isolated From Simarouba glauca Inhibits the Growth of Human Colorectal Carcinoma Cell Lines by Targeting Class-1 Histone Deacetylases

While anticancer properties of Simarouba glauca (SG, commonly known as Paradise tree) are well documented in ancient literature, the underlying mechanisms leading to cancer cell death begin to emerge very recently. The leaves of SG have been used as potential source of anticancer agents in traditional medicine. Recently attempts have been made to isolate anticancer agents from the leaves of SG using solvent extraction, which identified quassinoids as the molecules with tumoricidal activity. However, it is not known whether the anti-cancer potential of SG leaves is just because of quassinoids alone or any other phytochemicals also contribute for the potency of SG leaf extracts. Therefore, SG leaves were first extracted with hexane, chloroform, ethyl acetate, 70% ethanol, water and anti-cancer potential (for inhibiting colorectal cancer (CRC) cells HCT-116 and HCT-15 proliferation) determined using Sulforhodamine-B (SRB) assay. The chloroform fraction with maximal anticancer activity was further fractionated by activity-guided isolation procedure and structure of the most potent compound determined using spectral analysis. Analysis of the structural characterization data showed the presence of tricaproin (TCN). TCN inhibited CRC cells growth in a time- and dose dependent manner but not the normal cell line BEAS-2B. Mechanistically, TCN reduced oncogenic Class-I Histone deacetylases (HDACs) activity, followed by inducing apoptosis in cells. In conclusion, the anti-cancer potential of SG is in part due to the presence of TCN in the leaves