Mechanism of Tanreqing Injection in treatment of acute lung injury based on network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the mechanism of Tanreqing Injection in the treatment of acute lung injury(ALI) based on network pharmacology and molecular docking. The active components and action targets of Tanreqing Injection were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), PubChem, and SwissTargetPrediction databases, as well as available literature reports. The ALI-related targets were obtained from the GeneCards database and then mapped with Tanreqing Injection targets. Following the construction of "drug-component-potential target" network with Cytoscape 3.6.1, the potential targets were input into STRING to yield the protein-protein interaction(PPI) network, which was plotted using Cytoscape 3.6.1. Then the screened key targets were subjected to gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis based on DAVID database. The top three key targets RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB) and interleukin-6(IL6) were docked to the top three key compounds by PyMOL and AutoDock vina. A total of 58 active components of Tanreqing Injection, 597 corresponding targets and 503 common targets shared by Tanreqing Injection and ALI were fi-gured out, with the key targets AKT1, ALB and IL6 involved. GO and KEGG enrichment analysis yielded 1 445 biological processes and 148 signaling pathways, respectively. Molecular docking verified a good binding ability of the top three key targets to the top three key compounds. The analysis based on network pharmacology and molecular docking uncovered that Tanreqing Injection directly or indirectly regulated the pulmonary capillary endothelial cells and alveolar epithelial cells via anti-inflammation, thus alleviating ALI.

Moxibustion on the Governor Vessel for lung and kidney qi deficiency type in chronic obstructive pulmonary disease: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To observe the difference between the therapeutic effect of Du-moxibustion (Moxibustion on the Governor Vessel) combined with western medicine and that of simple western medication for the remission stage of chronic obstructive pulmonary disease.</p><p><b>METHODS</b>Two hundred and ten cases were randomly divided into an observation group (108 cases)and a control group (102 cases). The observation group was treated by routine treatment of western medicine combined with herb-partitioned spread moxibustion on the Governor Vessel between Dazhui (GV 14)and Yaoshu (GV 2). Simple western medicine was used in control group. The therapeutic effects of two groups were compared with the changes of symptom scores and pulmonary function before and after treatment.</p><p><b>RESULTS</b>The total effective rate of observation group (90.7%, 98/108) was higher than that of control group (74.5%, 76/102) (P < 0.01). The symptom scores and some pulmonary function indices such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the percentage of force expiratory volume in one second in predicted value(FEV1%) and maximal expiratory flow(PEF) after treatment were improved obviously than those before treatment in observation group (P < 0.05, P < 0.01), and the improvement degree was better than that of control group (all P < 0.01).</p><p><b>CONCLUSION</b>Moxibustion on the Governor Vessel combined with western medicine can improve the clinical symptoms and pulmonary function of chronic obstructive pulmonary disease of lung and kidney qi deficiency type effectively,and the effect is better than that of simple western medication.</p>

Experimental studies on anti-tumor angiogenesis effect of phosphodiesterase (PDE2, PDE4) inhibitors / 肿瘤

Objective: The purpose of our study was to investigate the effect of phosphodiesterase (PDE2 and PDE4) inhibitors on the proliferation and migration of endothelial cells as well as angiogenesis in vivo. Methods: Human umbilical vein endothelial cells (HUVEC) were selected for investigation of angiogenesis in vitro and the C57BL/6N mouse for in vivo study. The effects of PDE2 inhibitor [Erythro-9-(2-hydroxy-3nonyl) adenine, ENHA] and PDE4 inhibitor (RP705) on the intracellular cAMP levels in HUVEC were detected by enzyme-linked immunosorbant assay (ELISA) and their effects on the proliferation and migration of HUVEC were also determined. The tumor-inhibiting effects of combined application of ENHA and RP705 were observed. Results: EHNA (25 μmol/L) and RP705 (15 μmol/L) specifically inhibited the proliferation and migration of HUVEC stimulated by vascular endothelial growth factor (VEGF) and increased the intracellular cAMP level in HUVEC. EHNA combined with RP705 inhibited tumor angiogenesis in vivo. The tumor inhibitory rate was 45.50% in C57BL/6N mouse after combined therapy with EHNA and RP705. Conclusion: These results strongly suggested that PDE2 and PDE4 might be new potential therapeutic targets in pathological angiogenesis.

Feeding of mixed-carbon-resource during the expression phase in cultivation of recombinant Pichia pastoris expressing angiostatin / 生物工程学报

A recombinant strain of Pichia pastoris with a phenotype of Muts was used to produce angiostatin in a 5-L fermentor. The methanol utilization ability of the present strain was weak, which resulted in extremely low growth rate and angiostatin productivity during the expression phase with methanol as the sole carbon source. To enhance the cell density and angiostatin expression level, mixed-carbon-source of glycerol-methanol was used in the expression phase. The methanol concentration was well controlled at 5 g/L by a methanol sensor and control system, and glycerol was continuously fed into the fermentor to achieve a higher cell density. 120 g/L of cells and 39 mg/L of angiostatin were reached at the end of fermentation which lasted 110 h. The mean specific cell growth rate in the expression phase was 0.01 h(-1), and the mean specific angiostatin productivity was 0.006 mg/(g x h). According to the data obtained in several runs of fermentation in which glycerol was fed at different rates, a higher mean specific angiostatin productivity was reached at the mean specific cell growth rate of 0.012 h(-1). To avoid the repression of angiostatin expression caused by residual glycerol and ethanol accumulation due to overfeeding of glycerol, glycerol addition was controlled to produce continuous oscillations in dissolved oxygen, because the change of dissolved oxygen concentration could deliver the information of available carbon source in the fermentation broth. Controlled glycerol feeding also avoided the problem of oxygen limitation brought by high cell density, and thus decreased the cooling requirement of the fermentor. Cell density reached 150 g/L at the end of fermentation, and angiostatin level reached 108 mg/L after an expression period of 96 h when the mean specific growth rate was maintained at 0.012 h(-1) by using the glycerol feeding strategy to result in the oscillations in dissolved oxygen. The mean specific angiostatin productivity was improved to 0.02 mg/(g x h). The apparent cell yield on glycerol and methanol were respectively 0.69 g/g and 0.93 g/g, higher than those in the fermentation without using the feeding strategy with dissolved oxygen as the indicator of metabolism.