Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-β/SMAD and NF-κB signalling pathways.

Aims/hypothesis Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1 ) were tested in a mouse model of type 2 diabetic nephropathy.Electronic supplementary material The online version of this article

The quality of the design has been recognized as one of the key factors to the success of the engineering project. However, engineers need to repeatedly perform design tasks, such as processing information, to produce an appropriate design result. Such a design process involves many activities and lead into one or several iterative loops. Consequently, the sequence of performing design activities should be properly planned to avoid unnecessary loops. Design Structure Matrix (DSM) is one of the widely used methods to describe the design process. By employing DSM, the relationships and the sequence of the design activities can be identified. In this research, several principles of evaluating the design process are developed. In addition, fast messy Genetic Algorithm (fmGA) is employed along with the proposed evaluation principles and DSM to determine the optimal design process. Results show, based on the proposed evaluation principles, the impact of the iteration loops can be clearly identified. Furthermore, with the proposed optimization model and its computer implementation, engineers can find the optimal design process for the large-scale design project efficiently and effectively.