Anticancer β-hairpin peptides: membrane-induced folding triggers activity

Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells electronegative relative to the surface of noncancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but to preferentially fold at the surface of cancer cells, adopting an amphiphilic β-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charged membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma), and MDA-MB-436 (breast carcinoma). However, the cytotoxicity toward noncancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays, and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells.     

Synthesis, characterization and proton transport properties of mixed metal phosphonate-zirconium titanium hydroxy ethylidene diphosphonate

Novel hybrid material, zirconium titanium hydroxy ethylidene diphosphonate (ZTHEDP) of the class of tetravalent bimetallic acid (TBMA) salt was synthesized using sol-gel route. ZTHEDP was characterized for elemental analysis (zirconium, titanium and phosphorus by ICP-AES and carbon and hydrogen by CHN analyzer), spectral analysis (FTIR), thermal analysis (TGA), X-ray diffraction studies and SEM. Chemical resistivity of this material was assessed in various media-acids, bases and organic solvents. The protons present in the structural hydroxyl groups in ZTHEDP indicate good potential to exhibit solid state proton conduction. The proton transport property of ZTHEDP was explored by measuring specific conductance at different temperatures in the range of 303–423 K at 10 K intervals, using Solartron Impedance Analyzer (SI 1260) over a frequency range 1 Hz-32 MHz at a signal level below 1 V. Zirconium hydroxy ethylidene diphosphonate (ZrHEDP) and titanium hydroxy ethylidene diphosphonate (TiHEDP) were also synthesized under identical conditions, characterized and their proton transport properties investigated for comparative studies. It is observed that, in all cases, conductivity decreases with increasing temperature. Conductivity performance of ZTHEDP, ZrHEDP and TiHEDP is discussed based on conductivity data and activation energy. It is observed that, ZTHEDP exhibits enhanced conductance and the mechanism of transportation is proposed to be Grotthuss type.     

Trash GGBFS-based geopolymer as a novel sunlight-responsive photocatalyst for dye discolouration

In this study, we report a waste material-ground granulated blast furnace slag (GGBFS) as a low cost geopolymer, hybridised with ZnO to form a novel and efficient photocatalyst capable of discolouring textile wastewater. GGBFS is a waste material in an iron industry. Methylene blue was used as the probe dye and natural sunlight was used for activation of the photocatalyst. It was observed that under the experimental conditions, ZnGP-40 exhibited twice the discoloration efficiency than conventionally used ZnO or TiO₂. This enhanced performance is majorly attributed to increased surface area of ZnO when strewn in the GGBFS matrix. The photocatalysts were characterized by SEM, TEM, PSA, TGA, BET and UV–Vis/NIR. The effect of photocatalyst loading, speed of agitation and solar insolation has also been studied. Since this study has been performed in direct sunlight, it exhibits a realizable application of solar energy in the treatment of wastewater.     

Microwave assisted low temperature synthesis of sodium zirconium phosphate (NaZr<Subscript>2</Subscript>P<Subscript>3</Subscript>O<Subscript>12</Subscript>)

Sodium zirconium phosphate [NaZr₂P₃O₁₂], a potential ceramic matrix for fixation of high level nuclear waste, was synthesized by heating the mixture of sodium carbonate [Na₂CO₃], zirconyl nitrate hydrate [ZrO(NO₃)₂·5H₂O] and ammonium dihydrogen phosphate [NH₄H₂PO₄] in air, in a resistance heated furnace and a microwave heating system respectively in the temperature range 450 to 650°C. The mixture heated for 1 h in a resistance furnace at 450°C yielded a poorly crystalline NaZr₂P₃O₁₂ [NZP]. Increasing the temperature to 650°C produced a highly crystalline product. The same mixture heated in a microwave oven at 450°C for 1 h however, yielded the most crystalline NZP.In an alternate method, the mixture of sodium dihydrogen phosphate (NaH₂PO₄), zirconium dioxide (ZrO₂) and diammonium hydrogen phosphate [(NH₄)₂HPO₄] heated in resistance furnace at 650°C for the same period did not react in air. It also did not yield the pure product at 450°C when heated in microwave assembly for 1 h.The authors thank the Board of Research in Nuclear Sciences (BRNS) of the Department of Atomic Energy (DAE) for the financial support for this work under the project No. 2000/37/19/BRNS/1959 dtd09-02-02.     

Validation of LC/MS electrospray ionisation method for the estimation of ursodiol in human plasma and its application in bioequivalence study

A novel High Performance Liquid Chromatography-electrospray mass spectrometric method has been developed for the estimation of Ursodiol (Ursodeoxycholic acid)--a bile acid, in human plasma using Ornidazole as internal standard. The methodology involved solid phase extraction of the analyte from human plasma matrix. The chromatographic separation was achieved within seven minutes by an isocratic mobile phase containing 1.0 mM ammonium acetate and Acetonitrile (65:35, v/v), flowing through XTerra MS C18, 100 x 2.1, 3.5 microm analytical column, at a flow rate of 0.2 ml/min. Ion signals were measured in negative mode for Ursodiol and internal standard at m/z 391.3 and 278.1, respectively. A detailed validation of the method was performed as per USFDA guidelines and the standard curves were found to be linear in the range 50.0 ng/ml to 3000.0 ng/ml with the mean correlation coefficient more than 0.99. The absolute recovery was more than 54.90% for Ursodiol and 76.51% for internal standard. Ursodiol was stable for sixty-nine days at -70 degrees C and for eight hours at ambient temperature. After extraction from plasma, the reconstituted samples of Ursodiol were stable in autosampler at 10 degrees C for forty-eight hours. Upon subjecting to three freeze thaw cycles, there was no change in the recovery of the analyte. The integrity of the plasma samples remained unaffected even upon four-fold dilution with drug free human plasma. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. It was successfully applied to the pilot bioequivalence study of Ursodiol in male human subjects.     

Is combining meta‐GGA correlation functionals with the OPTX exchange functional useful?

The recent generalized gradient approximation (GGA) density functional OCS1 of Handy and Cohen is implemented in the deMon code and tested on a carefully selected set of problems. OCS1 is found to be accurate for molecular atomization energies, transition metal–ligand bonds, and systems with intramolecular hydrogen bonds. However, OCS1 encounters problems for systems with intermolecular hydrogen bonds. It also tends to elongate bond lengths systematically, and sometimes significantly. The OPTX exchange is combined with three meta‐GGA correlation functionals, Lap3, τ1, and τ2, the latter reported for the first time. The new meta‐GGA scheme OPTX exchange plus τ2 correlation called Oτ2 yields improved molecular geometries, NMR shielding constants, and an improved barrier height for the H+H₂ reaction. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Imaging the In Vivo Degradation of Tissue Engineering Implants by Use of Supramolecular Radiopaque Biomaterials

For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo‐tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain‐extended polycaprolactone (PCL2000‐U4U) elastomer and a novel iodinated bisurea‐modified CA additive (I‐U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE‐grafts are prepared by simply electrospinning a solution containing PCL2000‐U4U and I‐U4U. Rats receive an aortic interposition graft, either composed of only PCL2000‐U4U (control) or of PCL2000‐U4U and I‐U4U (test). The grafts are explanted for analysis at three time points over a 1‐month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo‐tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants.     

Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin

Free radicals, generally composed of reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated in the body by various endogenous and exogenous systems. The overproduction of free radicals is known to cause several chronic diseases including cancer. However, increased production of free radicals by chemotherapeutic drugs is also associated with apoptosis in cancer cells, indicating the dual nature of free radicals. Among various natural compounds, curcumin manifests as an antioxidant in normal cells that helps in the prevention of carcinogenesis. It also acts as a prooxidant in cancer cells and is associated with inducing apoptosis. Curcumin quenches free radicals, induces antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and upregulates antioxidative protein markers–Nrf2 and HO-1 that lead to the suppression of cellular oxidative stress. In cancer cells, curcumin aggressively increases ROS that results in DNA damage and subsequently cancer cell death. It also sensitizes drug-resistant cancer cells and increases the anticancer effects of chemotherapeutic drugs. Thus, curcumin shows beneficial effects in prevention, treatment and chemosensitization of cancer cells. In this review, we will discuss the dual role of free radicals as well as the chemopreventive and chemotherapeutic effects of curcumin and its analogues against cancer.     

Medium-size Gaussian basis sets for hydrogen through argon

Summary Medium-sized Gaussian basis sets are reoptimized for the ground states of the atoms from hydrogen through argon. The composition of these basis sets is (4s), (5s), and (6s) for H and He, (9s5p) and (12s7p) for the atoms Li to Ne, and (12s8p) and (12s9p) for the atoms Na to Ar. Basis sets for the² P states of Li and Na, and the³ P states of Be and Mg are also constructed since they are useful in molecular calculations. In all cases, our energies are lower than those obtained previously with Gaussian basis sets of the same size.