Fadwa Odeh

Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer

Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) is a herbal-derived drug with potential chemopreventive and chemotherapeutic activity. However, thymoquinone suffers from high hydrophobicity causing poor solubility which limits its bioavailability and high lipophilicity causing poor formulation characteristics. Liposomes are versatile drug carriers that can be used to solve problems of drug solubility, instability, and bio-distribution. In this study, we were able to prepare thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100 nm, and entrapment efficiency of more than 90% for TQ-LP and of 49.6% for XLP. The TQ-LP liposomes were effective in suppressing the proliferation of breast cancer cell lines MCF-7 and T47D, and at the same time exerting very low toxicity on normal periodontal ligament fibroblast. Altogether, this report describes the first successful encapsulation of thymoquinone into liposome; which maintains stability, improves bioavailability and maintains its anticancer activity.

Thymoquinone Efficiently Inhibits the Survival of EBV-Infected B Cells and Alters EBV Gene Expression

Epstein–Barr virus (EBV) is a human virus with oncogenic potentials that is implicated in various human diseases and malignancies. In this study, the modulator activity of the potent herbal extract drug thymoquinone on EBV was assessed in vitro. Thymoquinone was tested for cytotoxicity on human cells of lymphoblastoid cells, Raji Burkitt’s lymphoma, DG-75 Burkitt’s lymphoma, peripheral blood mononuclear cells, and periodontal ligament fibroblast. Apoptosis induction was analyzed via TUNEL assay and activity studies of caspase-3. The effect of thymoquinone on EBV gene expression was determined using real-time polymerase chain reaction. We report here, for the first time, a promising selective inhibitory affect of thymoquinone on EBV-infected B cell lines in vitro, compared with lower activity on EBV negative B cell line and very low toxicity on human peripheral blood mononuclear cells and periodontal ligament fibroblasts. Moreover, the drug was found to efficiently suppress the RNA expression of EBNA2, LMP1, and EBNA1 genes. Specifically, EBNA2 expression levels were the most affected indicating that this gene might have a major contribution to thymoquinone potency against EBV infected cells. Overall, our results suggest that thymoquinone has the potential to suppress the growth of EBV-infected B cells efficiently.

Self-Assembly Behavior of Benzotriazole in Water

The self-assembly behavior of 1H-benzotriazole (BTA) in aqueous solutions below its solubility limit has been revealed for the first time using NMR and light scattering techniques. Relaxation time, diffusion and chemical shift NMR techniques in addition to various light scattering techniques were used to study the aqueous behavior of 1H-Benzotriazole (BTA). These studies have revealed the self assembly of BTA molecules in water. Results show that BTA molecules tend to aggregate in water to form nanoparticles with radius in the range of 5 nm. The critical aggregation concentration (CAC) is estimated based on NMR data to be ∼16–20 mM. Such a critical aggregation concentration is comparable with the typical critical micelle concentration (CMC) for surfactants that have moderate aqueous solubility. The self-assembly behavior of BTA may not be limited to benzotriazole. It might be generally true for all poorly water soluble species to aggregate at concentrations below their solubility.

Selection and targeting of EpCAM protein by ssDNA aptamer

Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs. In this study, we have developed a ssDNA aptamer with high affinity and selectivity of targeting the EpCAM protein extracellular domain. The SELEX technique was applied and the resulted sequences were tested on EpCAM-positive human gastric cancer cell line, KATO III, and the EpCAM-negative mouse embryonic fibroblast, NIH/3T3 cells. Ep1 aptamer was successfully isolated and showed selective binding on EpCAM-positive KATO III cells when compared to EpCAM-negative NIH/3T3 cells, as observed by the flow cytometry and the confocal imaging results. Additionally, the binding of Ep1 to EpCAM protein was assessed using mobility shifting assay and aptamers-protein docking. Furthermore, the binding affinity of Ep1 was measured against EpCAM protein using EpCAM-immobilized on magnetic beads and showed apparent affinity of 118 nM. The results of this study could suggest that Ep1 aptamer can bind specifically to the cellular EpCAM protein, making it an attractive ligand for targeted drug delivery and as an imaging agent for the identification of cancer cells.

Jordan Conservation of Cultural Heritage in ERA

The Jordan Conservation of Cultural Heritage in ERA - JOCHERA project is aiming at overall reinforcement of University of Jordan (UJ), Hamdi Mango Center for Scientific Research (HMCSR) in Jordan cooperation capacities for cultural heritage protection research in the context of the European Research Area and development to the Conservation centre of excellence to respond to Jordans socio-economic needs. The JOCHERA impact will be increased capacities of the UJ in terms of (i) better research and innovation management, (ii) improved international Science & Technology cooperation and participation in FP7, (iii) enhanced cultural heritage protection research capacities, and (v) defined strategic development framework in order to increase UJ visibility and scope. Likewise, JOCHERA will increase research and innovation linkages within Jordan in particular with SMEs, enable better opportunities to young researchers and enhance EU-JO RTD cooperation landscape. The project duration is 24 months, started in 1st D...

Correction: Selection and targeting of EpCAM protein by ssDNA aptamer

[This corrects the article DOI: 10.1371/journal.pone.0189558.].

Medicine in Reverse

The axiom “all life is dependent on chemicals” is true but the chemicals must be the right kind and in the right proportions for healthy growth. A second truth is that “external or internal contact with chemicals in overdose concentrations may result in either discomfort, disease or in death”. Often the very therapeutic chemicals (medicines by any other name) created to reduce or eliminate one type of malady result in complications elsewhere in the body when taken accidently in too high dosage. Furthermore, overdoses of illegitimate drugs and exposure to biotoxins damage organs and may lead to death. Examples of some molecules commonly overdosed are shown in Fig. 11.1. This chapter gives fundamental and applied information on oil-in water microemulsion and on functionalized carrier particle colloids designed to selectively bind and physiologically deactivate in vivo several commonly overdosed chemicals. EKG and NMR techniques have been employed to obtain important diagnostic information.