Network Pharmacology-Based Analysis on the Effects and Mechanism of the Wang-Bi Capsule for Rheumatoid Arthritis and Osteoarthritis.

Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.

Flp, a Fis-like protein, contributes to the regulation of type III secretion and virulence processes in the phytopathogen Xanthomonas campestris pv. campestris.

The ability of the plant pathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on its ability to adapt quickly to the host environment during infection. Like most bacterial pathogens, Xcc has evolved complex regulatory networks that ensure expression and regulation of their virulence genes. Here, we describe the identification and characterization of a Fis-like protein (named Flp), which plays an important role in virulence and type III secretion system (T3SS) gene expression in Xcc. Deletion of flp caused reduced virulence and hypersensitive response (HR) induction of Xcc and alterations in stress tolerance. Global transcriptome analyses revealed the Flp had a broad regulatory role and that most T3SS HR and pathogenicity (hrp) genes were down-regulated in the flp mutant. ß-glucuronidase activity assays implied that Flp regulates the expression of hrp genes via controlling the expression of hrpX. More assays confirmed that Flp binds to the promoter of hrpX and affected the transcription of hrpX directly. Interestingly, the constitutive expression of hrpX in the flp mutant restored the HR phenotype but not full virulence. Taken together, the findings describe the unrecognized regulatory role of Flp protein that controls hrp gene expression and pathogenesis in Xcc.