Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.

Pigeon Pea (Cajanus cajan (L.) Millsp.) is a common food crop used in many parts of the world for nutritional purposes. One of its chemical constituents is cajanin stilbene acid (CSA), which exerts anticancer activity in vitro and in vivo. In an effort to identify molecular targets of CSA, we performed a kinome-wide approach based on the measurement of the enzymatic activities of 252 human kinases. The serine-threonine kinase WNK3 (also known as protein kinase lysine-deficient 3) was identified as the most promising target of CSA with the strongest enzymatic activity inhibition in vitro and the highest binding affinity in molecular docking in silico. The lowest binding affinity and the predicted binding constant pKi of CSA (−9.65 kcal/mol and 0.084 µM) were comparable or even better than those of the known WNK3 inhibitor PP-121 (−9.42 kcal/mol and 0.123 µM). The statistically significant association between WNK3 mRNA expression and cellular responsiveness to several clinically established anticancer drugs in a panel of 60 tumor cell lines and the prognostic value of WNK3 mRNA expression in sarcoma biopsies for the survival time of 230 patients can be taken as clues that CSA-based inhibition of WNK3 may improve treatment outcomes of cancer patients and that CSA may serve as a valuable supplement to the currently used combination therapy protocols in oncology.     

Biomaterials in cardiac tissue engineering: Ten years of research survey

Driven by enormous clinical need, myocardial tissue engineering has become a prime focus of research within the field of tissue engineering. Myocardial tissue engineering combines isolated functional cardiomyocytes and a biodegradable or nondegradable biomaterial to repair diseased heart muscle. The challenges in heart muscle engineering include cell related issues (such as scale up in a short timeframe, efficiency of cell seeding or cell survival rate, and immune rejection), the design and fabrication of myocardial tissue engineering substrates, and the engineering of tissue constructs in vitro and in vivo. Several approaches have been put forward, and a number of models combining various polymeric biomaterials, cell sources and bioreactors have been developed in the last 10 years for myocardial tissue engineering. This review provides a comprehensive update on the biomaterials, as well as cells and biomimetic systems, used in the engineering of the cardiac muscle. The article is organized as follows. A historic perspective of the evolution of cardiac medicine and emergence of cardiac tissue engineering is presented in the first section. Following a review on the cells used in myocardial tissue engineering (second section), the third section presents a review on biomaterials used in myocardial tissue engineering. This section starts with an overview of the development of tissue engineering substrates and goes on to discuss the selection of biomaterials and design of solid and porous substrates. Then the applications of a variety of biomaterials used in different approaches of myocardial tissue engineering are reviewed in great detail, and related issues and topics that remain challenges for the future progress of the field are identified at the end of each subsection. This is followed by a brief review on the development of bioreactors (fourth section), which is an important achievement in the field of myocardial tissue engineering, and which is also related to the biomaterials developed. At the end of this article, the major achievements and remaining challenges are summarized, and the most promising paradigm for the future of heart muscle tissue engineering is proposed (fifth section).     

Nanocomposite Elastomeric Biomaterials for Myocardial Tissue Engineering Using Embryonic Stem Cell‐derived Cardiomyocytes

Regeneration or repair of the damaged myocardium requires different strategies including engineered constructs for more efficient cell delivery. This study was undertaken to examine the potential of a new nanostructured elastomer to deliver embryonic stem cell‐derived cardiomyocytes (ESC‐CM) to an infarcted area of the myocardium. Engineered materials were biocompatible, mechanically stable, and elastomeric nanocomposites serving as substrates for delivery of ESC‐CM and as a left ventricular support device in myocardial regeneration strategies. Materials investigated were soft and strong poly(aliphatic/aromatic‐ester) multiblock thermoplastic elastomers with poly(ethylene terephthalate) (PET) hard segments and dimerized fatty acid, i.e., dilinoleic acid (DLA) soft segments, respectively, with and without addition of 0.2 wt% TiO₂ nanoparticles to form nanocomposites. The PET/DLA‐TiO₂ nanocomposite exhibited over 8 MPa tensile strength and 900% elongation at break. Addition of TiO₂ nanoparticles significantly altered surface roughness and enhanced adhesion and spreading of ESC‐CM derived from mouse and human embryonic stem cells. The newly developed materials did not affect the functional activity of spontaneously beating hESC‐CM, as demonstrated by unaltered rate of their beating, and the cells continued to demonstrate contractile activity on the materials for more than two months in culture (the longest time tested). Quantitative proliferation and survival assays using fibroblasts confirmed the ability of the new materials to support cells as well as or better than the present commercial‐type thermoplastic elastomer analog. The results indicate that PET/DLA and PET/DLA‐TiO₂ are promising candidates for the manufacture of engineered patches to deliver ESC‐CMs.     

Using mobile learning to increase environmental awareness

Mobile learning or m-learning, a relatively new concept, has attracted the interest of educators, researchers, and companies developing learning systems and instructional materials. This study investigated the use of integrating use of mobile technologies, data services, and multimedia messaging systems to increase students’ use of mobile technologies and to develop environmental awareness. Data was collected using “usefulness of mobile learning systems” questionnaire from a sample consisting of 20 male and 21 female undergraduates enrolled in computer education and instructional technologies classes at the Near East University in North Cyprus. Students voluntarily participated in a six-week program using mobile telephones to transmit photographs of local environmental blights and to exchange pictures and observations. Participants learned ways to maintain clean environments and increased their awareness of environmental concerns. Responses on questionnaire differed significantly based upon gender and grade.