Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study

Abstract: Background: A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. Objective: In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts. Methods: Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h. Results: Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy. Study limitations: Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required. Conclusion: This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid.

Establishment and evaluation of the Japanese edition of the Weekly Epidemiological Record (WER) website by the Faculty of Health Sciences of Kobe University School of Medicine.

To report on the establishment of the Japanese version website of the Weekly Epidemiological Record (WER) by the faculty and to evaluate its accessibility and the educational outcome: all articles from the WER since 2000 have been translated into Japanese by graduate students with teachers' guidance, verified by the committee members, and delivered to the website. The server log files and retrieval keywords were analyzed using Analog 6.0. An on-line questionnaire survey of visitors to the website was performed. Opinion sheets reported by the students for translation were evaluated as the educational outcome. Over 6 years, there were 820,571 requests to the website and, the number of requests increased with disease outbreaks. According to domain analysis, most requests were during daytime on weekdays, and the website was utilized by users in educational institutions and the Japanese government and by overseas visitors. Among respondents to the questionnaire, 47% were laypersons and 69% found the website easy to understand. SARS and HIV/AIDS were the terms most frequently used for retrieval. The students recognized the importance of the World Health Organization (WHO) and had broadened their perspective on international health. The website is useful for Japanese. The translating process was effective for international health education.