Search

Juanyong Zhao, Haiyang Liu, Ming Xia, Qian Chen, Lili Wan, Bin Leng, Chengyuan Tang, Guochun Chen, Yu Liu, Lei Zhang, Hong Liu Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Hong Liu; Lei Zhang, Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-13973116951 ; +86-18673174522, Email liuhong618@csu.edu.cn; zhanglei_xp@163.comPurpose: Accumulating clinical evidence showed that Tripterygium hypoglaucum (Lév.) Hutch (THH) is effective against IgA nephropathy (IgAN), but the mechanism is still unclear. This study is to evaluate the renal protective effect and molecular mechanism of THH against IgAN via network pharmacology, molecular docking strategy and experimental validation.Methods: Several databases were used for obtaining the active ingredients of THH, the corresponding targets, as well as the IgAN-related genes. The critical active ingredients, functional pathways, and potential for the combination of the hub genes and their corresponding active components were determined through bioinformatics analysis and molecular docking. The IgAN mouse model was treated with celastrol (1 mg/kg/d) for 21 days, and the aggregated IgA1-induced human mesangial cell (HMC) was treated with various concentrations of celastrol (25, 50 or 75 nM) for 48 h. The immunohistochemistry and Western blot techniques were applied to evaluate the protein expression of the predicted target. The cell counting kit 8 (CCK8) was used to detect HMC proliferation.Results: A total of 17 active ingredients from THH were screened, covering 165 IgAN-related targets. The PPI network identified ten hub targets, including PTEN. The binding affinity between the celastrol and PTEN was the highest (− 8.69 kJ/mol). The immunohistochemistry showed that celastrol promoted the expression of PTEN in the glomerulus of IgAN mice. Furthermore, the Western blot techniques showed that celastrol significantly elevated the expression of PTEN and inhibited PCNA and Cyclin D1 in vitro and in vivo. The CCK8 assay determined that celastrol decreased HMC proliferation in a concentration-dependent manner.Conclusion: This study suggests that activating PTEN by celastrol may play a pivotal role in THH alleviating IgAN renal injury.Keywords: IgA nephropathy, Tripterygium hypoglaucum (Lév.) Hutch, network pharmacology, molecular docking, celastrol, PTEN

Inefficient and ineffective management of technical product changes during ramp-up phases of new model ranges in series production endanger the defined time-to-market and, concurrently, a company's expected earnings. One of the research projects at the Bremen Institute of Industrial Technology and Applied Work Science at the University of Bremen deals with this topic, and, accompanied by industry, significant weaknesses with regard to the organizational aspects have been identified. Today's product change management processes are based on DIN 199/4, a German standard publicized by the German Institute for Standardization in 1981, which focuses on a documentation scheme for bills of materials as well as engineering drawings. Unfortunately, the management of a physical product change process is not described. The project, however, shows the organizational deficits in this area of research. This article points out the main weaknesses of today's product change management and proposes a new approach for a product change classification scheme as well as an approach for a new organization scheme for product change management teams in order to reduce product change implementation lead times. [ABSTRACT FROM AUTHOR]