Deciphering the Mechanism of YuPingFeng Granules in Treating Pneumonia: A Network Pharmacology and Molecular Docking Study.

Objective: YuPingFeng Granules (YPFGs) is an herbal formula clinically used in China for more than 100 years to treat pneumonia. Nevertheless, the mechanism of YPFG in pneumonia treatment has not been established. This network pharmacology-based strategy has been performed to elucidate active compounds as well as mechanisms of YPFG in pneumonia treatment. Methods: First, active compounds of YPFG were identified in the traditional Chinese medicine systems pharmacology (TCMSP) database, and then the targets related to the active compounds were obtained from TCMSP and Swiss Target Prediction databases. Next, using DisGeNET, DrugBank, and GeneCards databases, we got therapeutic targets of pneumonia and common targets between pneumonia targets and YPFG. After that, a protein-protein interaction (PPI) network of pneumonia composed of common targets was built to analyze the interactions among these targets, which focused on screening for hub targets by topology. Then, online software and the ClusterProfiler package were utilized for the enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) data. Finally, the visualization software of Autodock was used for molecular docking among the hub target proteins. Results: 10 hub genes were selected by comparing the GO and KEGG functions of pneumonia targets with those of the common targets of YPFG and pneumonia. By using molecular docking technology, a total of 3 active ingredients have been verified as being able to combine closely with 6 hub targets and contribute to their therapeutic effects. Conclusion: This research explored the multigene pharmacological mechanism of action of YPFG against pneumonia through network pharmacology. The findings present new ideas for studying the mechanism of action of Chinese medicine against pneumonia caused by bacteria.

A natural product targets BRD4 to inhibit phase separation and gene transcription.

The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.

Pathogenic Effects of Biofilm on Pseudomonas Aeruginosa Pulmonary Infection and Its Relationship to Cytokines.

BACKGROUND An animal (Sprague-Dawley rat) model of Pseudomonas aeruginosa biofilm associated with chronic pulmonary infection in vivo was established and the effects of the biofilm on P. aeruginosa and its relationship to cytokines were investigated. MATERIAL AND METHODS Biofilm of P. aeruginosa in alginate beads and planktonic PA0725 were purified by anion-exchange chromatograph. Sprague-Dawley (SD) rats were immunized with the biofilm and then inhaled the same strain of P. aeruginosa. Anti-biofilm antibody titer was detected using the enzyme linked immunosorbent assay (ELISA) method. The cell count and differential count in the bronchoalveolar lavage fluid (BALF) were measured. The levels of cytokines (IL-17, IL-1ß, MIP-2, and G-CSF) and tumor necrosis factor (TNF)-α in sera were also measured using an ELISA kit. RESULTS The sera anti-biofilm IgG antibody titer of immunized SD rats was increased significantly on the 5th and 8th days after inhalation. The IL-17 concentration was significantly higher on the 8th day after inhalation. The results indicated that when biofilm-pre-immunized rats were challenged with inhalation of PA0725 of P. aeruginosa, the biofilm acted as an antigen substance and mediated the antibody reaction of the antigen, which might cause serious airway inflammatory response and lung tissue injury. This effect may be related to IL-17. CONCLUSIONS P. aeruginosa biofilm protected the bacterium from antibiotics and might induce host immune damage in lung tissue and facilitate bacterium evading the host barrier.

A Natural Product from Polygonum cuspidatum Sieb. Et Zucc. Promotes Tat-Dependent HIV Latency Reversal through Triggering P-TEFb's Release from 7SK snRNP.

The latent reservoirs of HIV represent a major impediment to eradication of HIV/AIDS. To overcome this problem, agents that can activate latent HIV proviruses have been actively sought after, as they can potentially be used in combination with the highly active antiretroviral therapy (HAART) to eliminate the latent reservoirs. Although several chemical compounds have been shown to activate latency, they are of limited use due to high toxicity and poor clinical outcomes. In an attempt to identify natural products as effective latency activators from traditional Chinese medicinal herbs that have long been widely used in human population, we have isolated procyanidin C-13,3',3"-tri-O-gallate (named as REJ-C1G3) from Polygonum cuspidatum Sieb. et Zucc., that can activate HIV in latently infected Jurkat T cells. REJ-C1G3 preferentially stimulates HIV transcription in a process that depends on the viral encoded Tat protein and acts synergistically with prostratin (an activator of the NF-κB pathway) or JQ1 (an inhibitor of Brd4) to activate HIV latency. Our mechanistic analyses further show that REJ-C1G3 accomplishes these tasks by inducing the release of P-TEFb, a host cofactor essential for Tat-activation of HIV transcription, from the cellular P-TEFb reservoir 7SK snRNP.