Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

Background:Diabetic nephropathy(DN)is a serious complication of diabetes with rising prevalence worldwide.We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripterygium wilfordii.Methods:Celastrol-related targets were obtained from Herbal Ingredients’Targets(HIT)and GeneCards databases.DN-related targets were retrieved from GeneCards,DisGeNET,and Therapeutic Targets Database(TTD).A Protein-protein interaction(PPI)network was established using the Search Tool for the Retrieval of Interacting Genes(STRING)database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using ClusterProfiler.The cytoHubba plugin was used to select the top 10 hub targets.Molecular docking was performed employing PyMOL and AutoDock software.Cell counting kit-8(CCK-8)and flow cytometry assays were used to detect the viability and apoptosis of NRK-52E cells,respectively.The mRNA expression levels of mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),and AKT serine/threonine kinase 1(AKT1)in NRK-52E cells were assessed using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We obtained sixty-six overlapping targets of celastrol and DN.GO and KEGG analyses demonstrated that the core targets of celastrol and DN were mainly involved in the inflammatory and immune response,oxidative stress,advanced glycation end products(AGEs)and their receptors(RAGEs)(AGE-RAGE),TNF,interleukin 17(IL-17),and MAPK signaling pathways.Finally,based on the good binding activity with celastrol,MAPK3,TNF,and AKT1 were identified as the foremost targets of celastrol.We observed that celastrol enhanced the viability of high glucose(HG)-treated NRK-52E cells and inhibited apoptosis in the in vitro assays.Moreover,celastrol decreased the mRNA expression levels of MAPK3,TNF,and AKT1 in high glucose(HG)-treated NRK-52E cells.Conclusion:Celastrol may treat DN by targeting APK3,TNF,and AKT1 and regulating inflammatory responses and oxidative stress through the AGE-RAGE,TNF,IL-17,and MAPK signaling pathways.

Chinese herbal extract dl-3n-butylphthalide A commonly used drug for the treatment of ischemic stroke as a novel therapeutic approach to treat neurodegenerative diseases

DI-3n-butylphthalide is the active component isolated from the seeds of Apium graveolens Linn. A number of pharmacological and clinical studies have proven that dl-3n-butylphthalide is highly potent and multi-targeted with low toxicity and has a long time-window for the treatment of ischemic cerebrovascular disease. The mechanisms underlying dl-3n-butylphthalide include improving mitochondrial function and microcirculation, inhibiting apoptosis and reducing oxidative stress. Furthermore, dl-3n-butylphthalide may also be promising for the treatment of neurodegenerative diseases, such as Alzheimer＇s disease, vascular dementia and Parkinson＇s disease.

Organization and evolution of climate responsive strategies,used in Turpan vernacular buildings in arid region of China

Under the global crisis of energy shortage and environmental pollution,the climate responsive strategies used in vernacular buildings have attracted much attention for their potential to reduce energy consumption and carbon emissions.However,the relationships between these traditional climatic strategies were not precisely perceived,which may cause the inapplicability of these strategies for contemporary rural houses.In this paper,taking the Turpan vernacular buildings in arid region of China,the climate responsive strategies of buildings in the most significant periods such as the Gaochang period(before 1318),the Khanate and Republican period(1318–1949),the Modern period(1949–2010),and the Contemporary period(2011–present)were summarized.In addition,two different types of climatic strategies organizations,namely multilayer spaces and integrated building envelopes,were identified based on the temperature difference measurement and comparative analysis.The assessment of thermal performance of the organizations was conducted by the methodology of software simulation.Furthermore,the applicability of the organizations in rural areas was discussed,and a new combined organization was proposed.Consequently,this study can contribute to provide the main approaches for climatically responsive rural houses.

Viral MIPα homologous with human MIP-1α acts on HIV co-receptor CCR5

The function and usage of vMIPα encoded by K6 gene of herpesvirus 8 (HHV8) which has homology with human macrophage protein (MIP) have not been clearly known. In the present note the K6 gene of HHV8 was cloned and transfected into NIH3T3 cells and E. coli cells. Conditional media from the 3T3-transfected cells and K6 product vMIPa from E. coli. Cells were used to perform the experiments of ligand-receptor binding and cellular adhesion with peripheral blood macrophages. The conditional media and the purified vMIPa from E. coli could compete to bind to CCR5 located on macrophages from peripheral blood with I125-hMIP-1α chemokine of human. Cellular adhesion showed that the conditional media from transfected cells and the purified vMIPa did not induce the adhesion of macrophages from peripheral blood to ICAM-1. In conclusion, vMIPα encoded by K6 gene of HHV8 can bind to CCR5 of peripheral blood macrophage cells and does not induce their adhesion. This suggests that vMIPa enclosed CCR5, also known as HIV