Effect of curcumin on glioblastoma cells

Curcumin is a polyphenolic compound derived from Curcumin longa L. There are growing bodies of evidence revealing the antitumor effect of curcumin in different tumors; although the molecular mechanism behind this inhibition in glioblastoma multiform (GBM) still remains unclear. Here we investigated the antitumor activity of nano micelles curcumin compared with erlotinib in U-373 cells in monolayer cell cultures and spheroids models. Furthermore, we characterized affecting cell cycle perturbation, as well as apoptosis induction in GBM cells. The antiproliferative activity of nano micelles curcumin and erlotinib were assessed in monolayer and spheroid models. The influence of the cell cycle and expression levels of nuclear factor κB (NF-κB) and Wnt/β-catenin pathway was checked. Nano micelles curcumin suppressed cell growth in U-373 cells via modulation of Wnt and NF-κB pathways. Moreover, cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation posttreatment with nano micelles curcumin and erlotinib. In the core signaling pathways of GBM, nano micelles curcumin either significantly influences the NF-κB pathway by decreasing p-65 expression or significantly inhibits the Wnt/β-catenin pathway by declining cyclin D1 expression. In conclusion, we have shown that nano micelles curcumin effectively prevent proliferation, and invasion of GBM cells through perturbation of Wnt/β-catenin and NF-κB pathways, suggesting further investigations on the therapeutic application of this novel anticancer drug in in vivo models.     

Expression of HBsAg and preS2-S protein in different yeast based system: A comparative analysis

We have expressed both S and preS2-S genes coding for the hepatitis B small (S) and medium (M) proteins, respectively, in different yeast based expression systems and compared the production level of the recombinant proteins. In Saccharomyces cerevisiae, viral genes were expressed under the inducible Gal10/cyc1 and the constitutive PGK promoters using 2 μ replicating vectors. We showed that the yield of S protein was higher than M protein under both inducible (14.27 vs 10.9 mg/l) and constitutive (9.18 vs 6.39 mg/l) conditions, respectively. In the methylotrophic yeast Pichia pastoris, the viral genes were expressed in GS115 (Mut⁺: Methanol Utilizing) and KM71 (Mut^S: Methanol Utilizing Slow) under the control of the alcohol oxidase promoter (AOX1). In Mut^S background, both S and preS2-S genes were expressed at higher levels than in Mut⁺. In attempt to increase the yield of recombinant viral proteins in S. cerevisiae, we have co-expressed both inducible and constitutive vectors harboring the S or preS2-S genes leading to recombinant strains called UTS (containing pDP/S + pYePIT/S) and UTP (containing pDP/preS2-S + pYePIT/preS2-S). We showed that the recombinant S and preS2-S proteins were successfully detected and the production level reached 18.31 mg/l for the S and 13.22 mg/l for the M proteins.Our comparative study provides evidence that in small scale, S. cerevisiae is more suitable for HBsAg and preS2-S proteins production than P. pastoris under inducible rather than constitutive condition.     

Michael adducts of ascorbic acid as inhibitors of protein phosphatase 2A and inducers of apoptosis

Michael adducts of ascorbic acid with alpha,beta-unsaturated carbonyl compounds have been shown to be potent inhibitors of protein phosphatase 1 (PP1) without affecting cell viability at the respective concentrations. Here we were able to show that higher concentrations can partially inhibit PP2A activity and concomitantly induce apoptotic cell death. A nitrostyrene adduct of ascorbic acid proved to be a more potent and effective inhibitor of PP2A as well as a stronger inducer of apoptosis. These adducts only slightly lost their cytotoxic potential in multidrug resistant cells that were 10-fold less sensitive to apoptosis induction by okadaic acid and vinblastine.     

Arbuscular mycorrhizal symbiosis and abiotic stress in plants: A review

Abiotic stresses (such as salinity, drought, cold, heat, mineral deficiency and metals/metalloids) have become major threats to the global agricultural production. These stresses in isolation and/or combination control plant growth, development and productivity by causing physiological disorders, ion toxicity, and hormonal and nutritional imbalances. Some soil microorganisms like arbuscular mycorhizal fungi (AMF) inhabit the rhizosphere and develop a symbiotic relationship with the roots of most plant species. AMF can significantly improve resistance of host plants to varied biotic and abiotic stresses. Taking into account recent literature, this paper: (a) overviews major abiotic stresses and introduces the arbuscular mycorrhizae symbiosis (b) appraises the role and underlying major mechanisms of AMF in plant tolerance to major abiotic stresses including salinity, drought, temperature regimes (cold and heat), nutrient-deficiency, and metal/metalloids; (c) discusses major molecular mechanisms potentially involved in AMF-mediated plant-abiotic stress tolerance; and finally (d) highlights major aspects for future work in the current direction.     

Effect of bis [benzyl N'-(indol-3-ylmethylene)-hydrazinecarbodithioato]-zinc(II) derivatives on wound healing in Sprague Dawley rats

Effects of topical application of Bis[benzyl N'-(indol-3-ylmethylene)-hydrazinecarbodithioato]-zinc(II) (BHCZ) on wound healing and histology of healed wound were assessed. Sprague Dawley rats were experimentally induced wound in the posterior neck area. Tween 20 (0.2 ml of 10%) was applied to rats in Group 1 (negative control). Intrasite gel (0.2 ml) was applied topically to rats in Group 2 as reference. BHCZ at the concentrations 0.2 ml of 25, 50 and 100 mg/ml were applied to Group 3, 4 and 5, respectively. Wound dressed with BHCZ significantly healed earlier than those treated with 10% Tween 20. Also wound dressed with 100 mg/ml BHCZ accelerated the rate of wound healing compared to those dressed with intrasite gel and, 25 mg/ml and 50 mg/ml BHCZ. Histological analysis of healed wound with BHCZ showed comparatively less scar width at wound enclosure and the healed wound contained less macrophages and large amount of collagen with angiogenesis compared to wounds dressed with 10% Tween 20. Results of this study showed that wounds dressed with 100 mg/ml of BHCZ significantly enhanced acceleration of the rate of wound healing enclosure, and histology of healed wounds showed comparatively less macrophages and more collagen with angiogenesis.     

Effects of sphingolipids overload on red blood cell properties in Gaucher disease

Gaucher disease (GD) is a genetic disease with mutations in the GBA gene that encodes glucocerebrosidase causing complications such as anaemia and bone disease. GD is characterized by accumulation of the sphingolipids (SL) glucosylceramide (GL1), glucosylsphingosine (Lyso‐GL1), sphingosine (Sph) and sphingosine‐1‐phosphate (S1P). These SL are increased in the plasma of GD patients and the associated complications have been attributed to the accumulation of lipids in macrophages. Our recent findings indicated that red blood cells (RBCs) and erythroid progenitors may play an important role in GD pathophysiology. RBCs abnormalities and dyserythropoiesis have been observed in GD patients. Moreover, we showed higher SL levels in the plasma and in RBCs from untreated GD patients compared with controls. In this study, we quantified SL in 16 untreated GD patients and 15 patients treated with enzyme replacement therapy. Our results showed that the treatment significantly decreases SL levels in the plasma and RBCs. The increased SL content in RBCs correlates with abnormal RBC properties and with markers of disease activity. Because RBCs lack glucocerebrosidase activity, we investigated how lipid overload could occur in these cells. Our results suggested that SL overload in RBCs occurs both during erythropoiesis and during its circulation in the plasma.     

Preparation and characterization of micelles of oligomeric chitosan linked to all-trans retinoic acid

New amphiphilic chitosan derivatives of all trans retinoic acid-chitosan (RA-chitosan) with different molar feeding ratios of all trans retinoic acid (ATRA) were synthesized. The degree of ATRA substitution ranged from 8.72% to 18.78%. The RA-chitosan formed micelles with an average size of 142.14-208.4 nm, and zeta potential of +27.25 to 34.48 mV. The critical association concentration (CAC) was found to range from 1.3 × 10⁻² to 2.13 × 10⁻² mg ml⁻¹. Upon evaluation, the RA-chitosan shows no significant cytotoxicity on Hela and HepG2 cells. Analysis of micelles loaded with ATRA revealed that the size of micelles decreased by increasing loaded drug content while zeta potential did not change. ATRA was released slowly over 3-day period, and drug content had no effect on the release rate. These phenomena make RA-chitosan micelles as a candidate for drug carrier.     

Arbuscular mycorrhizal fungi regulate the oxidative system,hormones and ionic equilibrium to trigger salt stress tolerance in Cucumis sativus L.

Arbuscular mycorrhizal fungi (AMF) association increases plant stress tolerance. This study aimed to determine the mitigation effect of AMF on the growth and metabolic changes of cucumbers under adverse impact of salt stress. Salinity reduced the water content and synthesis of pigments. However, AMF inoculation ameliorated negative effects by enhancing the biomass, synthesis of pigments, activity of antioxidant enzymes, including superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase, and the content of ascorbic acid, which might be the result of lower level lipid peroxidation and electrolyte leakage. An accumulation of phenols and proline in AMF-inoculated plants also mediated the elimination of superoxide radicals. In addition, jasmonic acid, salicylic acid and several important mineral elements (K, Ca, Mg, Zn, Fe, Mn and Cu) were enhanced with significant reductions in the uptake of deleterious ions like Na+. These results suggested that AMF can protect cucumber growth from salt stress.     

In vitro evaluation of human osteoblast-like cell proliferation and attachment on nanostructured fluoridated hydroxyapatite

The effect of the fluorine content and nano-structure of fluoridated hydroxyapatite (FHA) on human osteoblast-like (HO) cell behavior were investigated. FHA nanopowders and bulk nanostructured FHA, produced via mechanical alloying and two-step sintering, respectively, were used. The cytotoxicity of FHA nanopowders was assessed by MTT. Cell attachment to the surface of the bulk nanostructured FHA was evaluated by culturing of HO cells. Although HO cells proliferated 10 % more in contact with FHA nanopowders compared to culture medium without FHA nanopowders, an increase in the fluorine content of FHA caused a delay in the cell proliferation by about 2 days. Cell attachment on the bulk nanostructured FHA did not change the fluorine content.