SAR Studies on the Inhibitors for the Treatment of Inflammatory Diseases

School of Molecular Sciences(Chemistry)Inflammation is defensive host response that occurs from infection and injury and the inflammatory process is the pivotal physiological response of our body and essential part of the human physiology. Due to the mechanistic relationship between chronic diseases and inflammation, a better understanding for the molecular mechanism of chronic inflammation could attenuate cellular inflammation pathways. Under inflammatory pathways, the impetus of proinflammatory mediators usually caused by the increased expression of transcriptional factors which is also a potential targets in the development of novel and effective anti-inflammatory therapeutics. Among others, we are interested in the Nuclear Factor Kappa-B (NF-??B) which is reported as a major mediator that regulates inflammatory gene expression and also decrease the prevalence of inflammation responses. To suppress the inflammatory activity, inhibitors that could selectively target this protein are needed. We therefore, chose the natural product cerulenin which has been studied widely because of its antifungal and antibacterial properties, for designing inhibitors. In light of the interesting inhibitory properties displayed by cerulenin for fatty acid synthase (FASN), we were keen to explore the possible binding mode of this natural product with a view to design various derivatives that would be amicable to synthetic manipulation in order to enable SAR studies. Potent analogues of cerulenin, with various chain lengths and substitutions, are synthesized and evaluated for their ability to inhibit NF-??B enhanceosome. Taken together, by identifying target protein with constructed inhibitors derived from cerulenin might give revolutionary effect on discovering new therapeutic agents.ope

Design and Implementation of a Wireless Charging-Based Cardiac Monitoring System Focused on Temperature Reduction and Robust Power Transfer Efficiency

Wireless power transfer systems are increasingly used as a means of charging implantable medical devices. However, the heat or thermal radiation from the wireless power transfer system can be harmful to biological tissue. In this research, we designed and implemented a wireless power transfer system-based implantable medical device with low thermal radiation, achieving 44.5% coil-to-coil efficiency. To suppress thermal radiation from the transmitting coil during charging, we minimized the ESR value of the transmitting coil. To increase power transfer efficiency, a ferrite film was applied on the receiving part. Based on analyses, we fabricated a cardiac monitoring system with dimensions of 17 x 24 x 8 mm(3) and implanted it in a rat. We confirmed that the temperature of the wireless charging device increased by only 2 degrees C during the 70 min charging, which makes it safe enough to use as an implantable medical device charging system.11Ysciescopu

Effect of corticosteroids during ongoing drug exposure in pantoprazole-induced interstitial nephritis

Acute interstitial nephritis (AIN) represents a significant cause of acute renal failure in hospital practice. An increasing number of drugs are known to cause AIN. Due to the lack of prospective, randomized clinical trials, the most effective management is still uncertain, especially the role of steroids in the resolution of interstitial nephritis remains to be further defined. We report on a case with pantoprazole-induced interstitial nephritis and on the effect of steroids during ongoing drug exposure. In spite of ongoing drug exposure, steroids led to almost complete resolution of the inflammatory infiltrates. Early diagnosis of interstitial nephritis by renal biopsy and identification of the causative drug and its withdrawal remains the mainstay of treatment. However, the additional use of steroids has the potential to eradicate inflammatory infiltrates more rapidly and completely and may thus be important to minimize subsequent chronic damag

Microspinning: Local Surface Mixing via Rotation of Magnetic Microparticles for Efficient Small-Volume Bioassays

The need for high-throughput screening has led to the miniaturization of the reaction volume of the chamber in bioassays. As the reactor gets smaller, surface tension dominates the gravitational or inertial force, and mixing efficiency decreases in small-scale reactions. Because passive mixing by simple diffusion in tens of microliter-scale volumes takes a long time, active mixing is needed. Here, we report an efficient micromixing method using magnetically rotating microparticles with patterned magnetization induced by magnetic nanoparticle chains. Because the microparticles have magnetization patterning due to fabrication with magnetic nanoparticle chains, the microparticles can rotate along the external rotating magnetic field, causing micromixing. We validated the reaction efficiency by comparing this micromixing method with other mixing methods such as simple diffusion and the use of a rocking shaker at various working volumes. This method has the potential to be widely utilized in suspension assay technology as an efficient mixing strategy