Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.     

Molecular and Supramolecular Structural Studies on Significant Repetitive Sequences of Resilin

Resilin is a member of the family of elastomeric proteins and is found in specialised regions of the cuticle of most insects, and provides low stiffness, high strain and efficient energy storage. It is best known for its role in insect flight and the remarkable jumping ability of fleas and spittle bugs. In common with other elastomeric proteins, the recently identified Drosophila melanogaster proresilin shows glycine‐rich repetitive sequences; in particular the N‐ and C‐terminal regions of the protein are dominated by 18 repeats of a 15‐residue sequence (SDTYGAPGGGNGGRP) and eleven repeats of a 13‐residue sequence (GYSGGRPGGQDLG), respectively. We synthesised and analysed the molecular and supramolecular structure of some polypeptides with sequences belonging to the glycine‐rich repeated domain of D. melanogaster resilin. The conformational studies performed by CD, FTIR and NMR spectroscopies pointed to the coexistence of two main conformational features, such as folded β‐turns and (quasi)extended structures (e.g., poly‐L ‐proline II conformation) in common with other elastomeric proteins; this suggests an elasticity mechanism for resilin common to other elastomeric proteins. Our data show that also in the case of resilin, repetitive sequences are characterised by autonomous structures almost independent of the remaining parts of the molecule as already extensively found for elastin. From a supramolecular point of view, a great tendency to aggregate in fibrous structures is observed, particularly for the resilin‐ inspired polypeptide (PGGGN)₁₀. This is encouraging for the development of resilin‐based biomaterials for the production of biocompatible medical devices, as well as high performing elastic materials.     

Biodiesel resources and production technologies – A review

The environmental concern and availability of fuels are greatly affecting the trends of fuels for transportation vehicles. Biodiesel is one of the options as alternative transport fuel. This can be produced from straight vegetable oils (SVOs), oils extracted from various plant species and animal fats. Amongst many resources, availability and cost economy are the major factors affecting the large scale production of the biodiesels. The transesterification is one of the production processes for biodiesel, but incomplete esterification of all fatty acids in the starting material, lengthy purification methods such as water washing, relatively long reaction times, contamination and separation difficulties associated with co-production of glycerol and saponification of the starting material under certain reaction conditions are still being major challenges in the biodiesel production. Technological advancement and enhanced production methods are the demand of present time for large scale and sustainable production of biodiesel. In the present paper, comprehensive review on its production process, feed stock and its applications have been made. From many case studies it was concluded that engine performance with B20 biodiesel blends, and mineral diesel were found comparable.     

Permeation and skin retention of quercetin from microemulsions containing Transcutol® P

A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol(?) P as solubilizing agent and permeation enhancer, was emulsified with Labrafil(?) as oil phase and Labrasol(?)/Capryol(?) 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz's cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol(?) P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol(?) P. These two last formulations are those showing the lower skin retention.     

Tuning polycaprolactone-carbon nanotube composites for bone tissue engineering scaffolds

This report describes the mechanical, thermal and biological characterisation of a solid free form microfabricated carbon nanotube-polycaprolactone composite, in which both the quantity of nanotubes in the matrix as well as the scaffold design were varied in order to tune the mechanical properties of the material. The creep and stress relaxation behaviour of the composite material was analysed to identify an optimal composition for bone tissue engineering. Moreover, the morphology and viability of osteoblast-like cells (MG63) on composite scaffolds were analysed using scanning electron microscopy and MTT assays. Our data demonstrate that by changing the ratio of CNT to PCL, the elastic modulus of the nanocomposite can be varied between 10 and 75 MPa. In this range, the geometry of the scaffold can be used to finely tune its stiffness. However our PCL-CNT nanocomposites were able to sustain osteoblast proliferation and modulate cell morphology. Thus we show the potential of custom designed CNT nanocomposites for bone tissue engineering.     

DNA Binding Ellipticine Analogues: Synthesis,Biological Evaluation,and Structure–Activity Relationships

Novel angular and branched ellipticine‐correlated anticancer agents were developed. In particular, compound 24 , with two basic side chains on opposite sides of the molecule, exhibits cytotoxicity in the nanomolar range, acting as a DNA intercalator and topoisomerase II inhibitor. SAR studies with pyridocarbazole derivatives in comparison with corresponding smaller pyrroloquinolines are discussed.

     

Dynamic Light: The Media Facades of realities:united

Valentina Croci reviews the recent work of realities:united, who first came into the spotlight in 2003 with their media facade for the Kunsthaus Graz. She highlights how recent projects, such as the Crystal Mesh for the Iluma Building in Singapore and the exterior of the C4 in Cordoba, Spain, transcend the notion of the digital facade as billboard. Lighting is dynamically applied, in order to enhance the three-dimensional experience of architecture rather than to flatten it. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparative Investigation on Acid Hydrolysis of Sweet Potato Starches with Different Amylopectin Chain‐Length

The solubilization of starch from the new sweet potato cultivar “Quick Sweet” (QS) in 2.2 M aqueous HCl occurred at a much higher rate than that from normal sweet potato (NS). QS starch has an abnormal amylopectin chain‐length distribution with an unusually high percentage of short side‐chains. Two‐stage hydrolysis occurred in both cases. The apparent first‐order kinetic constants (k) were calculated for both stages of the hydrolytic process in both types of sweet potato starch. A more drastic difference between the investigated starches (k for QS and NS starches was 27.0×10^‐2 d^‐1 and 7.0×10^‐2 d^‐1, respectively) was observed for the first stage of the hydrolysis affecting the amorphous regions of starches whereas the rate for the second stage (the degradation of the crystalline part) for the starch from QS was only slightly higher. The role of the structural defectiveness of QS in decreasing the granular resistance to acid hydrolysis and increasing the absorptive properties of the granules for water molecules is discussed.