Mitochondria targeting peptides for highly efficient cancer therapy

Department of ChemistrySynthesis of Cyclic mitochondria penetrating peptides (MPPs) coordinated with Ir(III) complex and pH-responsive charge conversion MPPs , 2016, Jae-Hyeong Park, Graduate Program of Chemistry, Ulsan National Institute of Science and Technology(UNIST). Selectively targeting and accumulating the photosensitizers (PS) inside the cancer cells have considerable interest. Herein, we report simple, biocompatible and robust technique for the conjugation of iridium to the MPPs complexes to target the mitochondria of cancer cells. While considering the organelle specific targeting, the mitochondria have received vital merits, upon their ability to induce apoptosis and they become an ideal target for several PDT agents. Cyclic [HK(Fxr)nH] and corresponding linear peptide [K(Fxr)nHH] were conjugated with Ir(III) complexes[Red and Green]. Ir(III) complexes and histidine (His) which has positively charged amino acid can easily bind through coordination between imidazole side chain of histidine (His) and metal which is highly efficient and easily synthesized through cyclization procedure. As a result, this effectively develop designed strategy for PDT agent based on Ir(III) complexes, which specifically targeted the mitochondria. Moreover, this cyclic modified complexes showed an improved PDT effect compared to linear one, meaning of a potent mitochondria-targeted PDT agents in antitumor therapy. Although both forms possess abundant charge, cyclic structure with rigidity is ability to result in an ideal interface for interaction with membrane constituent more than flexible structure. Stimuli responsive degradation of chemical bonds are useful tools for the development of ???smart materials??? which have remarkable applications in stimuli responsive drug delivery system. The pH is commonly applied to the cancer specific drug delivery system, because the pH near the tumor or in the tumor extracellular environment significantly acidic as pH 6-6.5 while the normal physiological pH is around 7.4. In this study, we designed and developed mitochondria targeting short peptide with charge conversion depending on pH values. The peptide sequences consists of FxrFxKK, possess positive charge and lipophilic character for targeting mitochondria. We conjugated drug (PU-10-COOH) as an inhibitor of HSP90 and maleic derivatives which are play a role of hydrolyzed in MPPs. Once maleic conjugated MPP extravagates into cell membrane through highly permeability, amide bonds within conjugate occur hydrolysis, reproducing intrinsic properties of MPP in the acidic tumor extracellular fluids (pH < 7) for cellular uptake and mitochondria targeting. Moreover, this platforms shows anticancer effect at 20 ??M concentration. Therefore, we hope that this model conjugated peptides have a potent of cancer therapy agent.ope

Smeared BTZ Black Hole from Space Noncommutativity

We study a novel phenomena of smearing of black hole horizons from the effect of space noncommutativity. We present an explicit example in $AdS_3$ space, using the Chern-Simons formulation of gravity. This produces a smeared BTZ black hole which goes beyond the classical spacetime unexpectedly and there is {\it no} reality problem in our approach with the gauge group $U(1,1) \times U(1,1)$. The horizons are smeared, due to a splitting of the Killing horizon and the apparent horizon, and there is a metric signature change to Euclidean in the smeared region. The inner boundary of the smeared region acts as a trapped surface for timelike particles but the outer as a classical barrier for ingoing particles. The lightlike signals can escape from or reach the smeared region in a {\it finite} time, which indicates that {\it the black hole is not so dark, even classically.} In addition, it is remarked that the Hawking temperature can {\it not} be defined by the regularity in the Euclidean geometry except in the non-rotating case, and the origin can be smeared by a {\it new} (apparent) horizon.Comment: Added notes about boundary conditions, NC curvature, and torsion; Accepted in JHE

The Role of Echocardiography in Evaluating Cardiovascular Diseases in Patients with Diabetes Mellitus

Patients with diabetes mellitus are highly susceptible to cardiovascular complications, which are directly correlated with cardiovascular morbidity and mortality. In addition to coronary artery disease, there is growing awareness of the risk and prevalence of heart failure (HF) in patients with diabetes. Echocardiography is an essential diagnostic modality commonly performed in patients with symptoms suggestive of cardiovascular diseases (CVD), such as dyspnea or chest pain, to establish or rule out the cause of symptoms. Conventional echocardiographic parameters, such as left ventricular ejection fraction, are helpful not only for diagnosing CVD but also for determining severity, treatment strategy, prognosis, and response to treatment. Echocardiographic myocardial strain, a novel echocardiographic technique, enables the detection of early changes in ventricular dysfunction before HF symptoms develop. This article aims to review the role of echocardiography in evaluating CVD in patients with diabetes mellitus and how to use it in patients with suspected cardiac diseases