Magnolol (Mag), an active constituent isolated from the Chinese herb Hou p'u (Magnolia officinalis) has long been used to suppress inflammatory processes. Chronic inflammation is well known to be involved in vascular injuries such as atherosclerosis in which interleukin (IL)-6 may participate. Signal transducer and activator of transcription protein 3 (STAT3), a transcription factor involved in inflammation and the cell cycle, is activated by IL-6. In this study, we evaluated whether Mag can serve as an anti-inflammatory agent during endothelial injuries. The effects of Mag on IL-6-induced STAT3 activation and downstream target gene induction in endothelial cells (ECs) were examined. Pretreatment of ECs with Mag dose dependently inhibited IL-6-induced Tyr705 and Ser727 phosphorylation in STAT3 without affecting the phosphorylation of JAK1, JAK2, and ERK1/2. Mag pretreatment of these ECs dose dependently suppressed IL-6-induced promoter activity of intracellular cell adhesion molecule (ICAM)-1 that contains functional IL-6 response elements (IREs). An electrophoretic mobility shift assay (EMSA) revealed that Mag treatment significantly reduced STAT3 binding to the IRE region. Consistently, Mag treatment markedly inhibited ICAM-1 expression on the endothelial surface. As a result, reduced monocyte adhesion to IL-6-activated ECs was observed. Furthermore, Mag suppressed IL-6-induced promoter activity of cyclin D1 and monocyte chemotactic protein (MCP)-1 for which STAT3 activation plays a role. In conclusion, our results indicate that Mag inhibits IL-6-induced STAT3 activation and subsequently results in the suppression of downstream target gene expression in ECs. These results provide a therapeutic basis for the development of Mag as an anti-inflammatory agent for vascular disorders including atherosclerosis.
Rationale & Objective: Hemodialysis facilities are high-risk environments for the spread of hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model. Study Design: Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists, and public health practitioners. Setting & Participants: All dialysis patients in Changhua County, Taiwan were treated using an interdisciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C). Quality Improvement Activities: Provision of an HCV care cascade to fill 3 gaps, including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau. Outcome: Outcome measures included quality indicators pertaining to 6 steps in HCV care ranging from HCV screening to treatment completion to cure. Analytical Approach: A descriptive analysis. Results: A total of 3,657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 166 (96.0%) of 173 patients.No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferonbased therapy (2017) to 25.6% after restricted provision of DAA (2017DAA ( -2018, and then to 89.1% after universal access to DAA (2019).Limitations: Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease.Conclusions: A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization.Complete author and article information provided before references.
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