Synthesis and in vitro evaluation of novel 1,2,4-triazine derivatives as neuroprotective agents

The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H₂O₂-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-κB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H₂O₂, was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases.     

Biodiesel production via transesterification of palm olein using waste mud crab (Scylla serrata) shell as a heterogeneous catalyst

A recent rise in crab aquaculture activities has intensified the generation of waste shells. In the present study, the waste shells were utilized as a source of calcium oxide to transesterify palm olein into methyl esters (biodiesel). Characterization results revealed that the main component of the shell is calcium carbonate which transformed into calcium oxide when activated above 700 °C for 2 h. Parametric studies have been investigated and optimal conditions were found to be methanol/oil mass ratio, 0.5:1; catalyst amount, 5 wt.%; reaction temperature, 65 °C; and a stirring rate of 500 rpm. The waste catalyst performs equally well as laboratory CaO, thus creating another low-cost catalyst source for producing biodiesel. Reusability results confirmed that the prepared catalyst is able to be reemployed up to 11 times. Statistical analysis has been performed using a Central Composite Design to evaluate the contribution and performance of the parameters on biodiesel purity.     

Bisleuconothine A,an eburnane–aspidosperma bisindole alkaloid from Leuconotis griffithii

A new bisindole alkaloid, bisleuconothine A (1) consisting of an eburnane–aspidosperma type skeleton, was isolated from the bark of Leuconotis griffithii. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and X-ray analysis. Bisleuconothine A (1) showed cell growth inhibitory activity against various human cancer cell lines.     

Electronic, ductile, phase transition and mechanical properties of Lu-monopnictides under high pressures

The structural, elastic and electronic properties of lutatium-pnictides (LuN, LuP, LuAs, LuSb, and LuBi) were analyzed by using full-potential linearized augmented plane wave within generalized gradient approximation in the stable rock-salt structure (B1 phase) with space group Fm-3m and high-pressure CsCl structure (B2 phase) with space group Pm-3m. Hubbard-U and spin-orbit coupling were included to predict correctly the semiconducting band gap of LuN. Under compression, these materials undergo first-order structural transitions from B1 to B2 phases at 241, 98, 56.82, 25.2 and 32.3 GPa, respectively. The computed elastic properties show that LuBi is ductile by nature. The electronic structure calculations show that LuN is semiconductor at ambient conditions with an indirect band gap of 1.55 eV while other Lu-pnictides are metallic. It was observed that LuN shows metallization at high pressures. The structural properties, viz, equilibrium lattice constant, bulk modulus and its pressure derivative, transition pressure, equation of state, volume collapse, band gap and elastic moduli, show good agreement with available data.

Protective role of curcumin in ameliorating AFB1-induced apoptosis via mitochondrial pathway in liver cells

It is well documented that liver is the primary target organ of aflatoxin B₁ (AFB₁) and curcumin proved to be effective against AFB₁-induced liver injury. In the present study, we investigated the preventive effects of curcumin against AFB₁-induced apoptosis through the molecular regulation of p53, caspase-3, Bax, caspase-9, Bcl-2 and cytochrome-C associated with mitochondrial pathway. Liver antioxidant levels were measured. The hallmarks of apoptosis were analysed by methyl green-pyronin-Y staining, transmission electron microscopy, RT-PCR and western blot. Results revealed that dietary curcumin ameliorated AFB₁-induced oxidative stress in a dose-dependent manner. Methyl green-pyronin-Y staining and transmission electron microscopy showed that AFB₁ induced apoptosis and caused abnormal changes in liver cells morphology such as condensation of chromatin material, reduces cell volume and damaged mitochondria. Moreover, mRNA and protein expression results manifested that apoptosis associated genes showed up-regulation in AFB₁ fed group. However, the supplementation of dietary curcumin (dose-dependently) alleviated the increased expression of the apoptosis associated genes at mRNA and protein level, and restored the hepatocytes normal morphology. The study provides an insight and a better understanding of the preventive mechanism of curcumin against AFB₁-induced apoptosis in hepatocytes and provide scientific basis for the therapeutic uses of curcumin.

     

Structure and Stability Analysis of Cytotoxic Complex of Camel α-Lactalbumin and Unsaturated Fatty Acids Produced at High Temperature

Abstract

α-Lactalbumin (α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and a-La -linoleic acid complexes were generated by adding fatty acid to camel holo a-La at 60°C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces a-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La- LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-0A-60 < α-La. La-0A-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-0A-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-0A-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.     

Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

Glioblastoma multiform (GBM) is known as an aggressive glial neoplasm. Recently incorporation of mesenchymal stem cells with anti-tumor drugs have been used due to lack of immunological responses and their easy accessibility. In this study, we have investigated the anti-proliferative and apoptotic activity of atorvastatin (Ator) in combination of mesenchymal stem cells (MSCs) on GBM cells in vitro and in vivo. The MSCs isolated from rats and characterized for their multi-potency features. The anti-proliferative and migration inhibition of Ator and MSCs were evaluated by MTT and scratch migration assays. The annexin/PI percentage and cell cycle arrest of treated C6 cells were evaluated until 72 h incubation. The animal model was established via injection of C6 cells in the brain of rats and subsequent injection of Ator each 3 days and single injection of MSCs until 12 days. The growth rate, migrational phenotype and cell cycle progression of C6 cells decreased and inhibited by the interplay of different factors in the presence of Ator and MSCs. The effect of Ator and MSCs on animal models displayed a significant reduction in tumor size and weight. Furthermore, histopathology evaluation proved low hypercellularity and mitosis index as well as mild invasive tumor cells for perivascular cuffing without pseudopalisading necrosis and small delicate vessels in Ator?+?MSCs condition. In summary, Ator and MSCs delivery to GBM model provides an effective strategy for targeted therapy of brain tumor.