Effect of TU-100 in NASH

Background : Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut–liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model. Methods : Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance. Results : At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P < 0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72% ; P = 0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P < 0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P < 0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P < 0.05). Conclusions : TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model

Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100)

Medications or dietary components can affect both the host and the host’s gut microbiota. Changes in the microbiota may influence medication efficacy and interactions. Daikenchuto (TU-100), a herbal medication, comprised of ginger, ginseng, and Japanese pepper, is widely used in Japanese traditional Kampo medicine for intestinal motility and postoperative paralytic ileus. We previously showed in mice that consumption of TU-100 for 4 weeks changed the gut microbiota and increased bioavailability of bacterial ginsenoside metabolites. Since TU-100 is prescribed in humans for months to years, we examined the time- and sex-dependent effects of TU-100 on mouse gut microbiota. Oral administration of 1.5% TU-100 for 24 weeks caused more pronounced changes in gut microbiota in female than in male mice. Changes in both sexes largely reverted to baseline upon TU-100 withdrawal. Effects were time and dose dependent. The microbial profiles reverted to baseline within 4 weeks after withdrawal of 0.75% TU-100 but were sustained after withdrawal of 3% TU-100. In summary, dietary TU-100 changed mouse microbiota in a time-, sex-, and dose-dependent manner. These findings may be taken into consideration when determining optimizing dose for conditions of human health and disease with the consideration of differences in composition and response of the human intestinal microbiota

産学連携知的財産管理室 : 2016年度活動報告

2016年度川崎医科大学内に産学連携知的財産管理室が発足した。2014年度からINPIT（独立行政法人工業所有権情報・研修館）のアドバイザー派遣事業により，広域大学知的財産アドバイザー（学内としては参与）を２年間招聘することが可能となり，川崎学園の３大学と岡山県立大学ならびに福山大学でネットワーク（NW）を形成した西日本医系大学知的財産管理NW事業が展開され，産学連携知的財産管理の基盤整備が充実した。この発足は，2016年度からプロジェクト形成支援型NWとして新たに採択されたことを受けたものである。産学官連携と知的財産管理の全般を所掌するとともに，学内ではFD会の開催，BioJapanを中心とする学内研究シーズの紹介，川崎医科大学初の産学連携を推進する展示会のKMSメディカル・アークの開催，シーズ集発刊，WEBの開設を実施した。さらに，東京医科歯科大学が主幹校となっている医学系産学連携ネットワーク協議会や，中国地域産学官連携コンソーシアムに参画するとともに，岡山県内の産学官連携クラスターでの活動を展開した。また，その他の産学官連携の組織団体の開催するセミナー等にも参加して情報収集に努めた。2016年度の産学連携知的財産管理室の活動を報告し，今後の展開についても考案する。The industry-academia collaboration and intellectual property management section was established within Kawasaki Medical School since fiscal year 2016. From fiscal 2014, it became possible to invite a wide-area university intellectual property advisor (participate as a campus) for 2 years by the advisor dispatch program by INPIT (National Center for Industrial Property Information and Training), and three univercities (Kawasaki Medical School, Kawasaki Medical and Welfare University and Kawasaki College of allied Health Professions) in Kawasaki Gakuen (an educational foundation) with Okayama Prefectural University and Fukuyama University formed West-Japan Medical Network for Intellectual Property Management project. Thereafter, new project for inviting advisor from INPIT was adopted since 2016. This new project is project formassisted program. At the same time, industry-academia collaboration and intellectual property management section in Kawasaki Medical School started its activities such as held facultydeveloping meeting, introduction of research seeds in our medical school in domestic exhibitions (i.e., BioJapan), open an exhibition called “KMS Medical-Ark" and publishing booklet for disclosure of research seeds. Inaddition with these activities, our section is participating nation level net-work such as the Japanese Association of Medical University Network for technology Transfer (medUnet) managed by Tokyo Medical and Dental University as well as several Okayama prefectural clusters for industry-academia collaboration, especially medical and engineering. In this article, activities of our section in fiscal year 2016 were shown and future outlook is discussed

産学連携知的財産管理室 : 2017年度から2018年度半ばまでの報告

　2016年度より川崎医科大学内に発足した産学連携知的財産管理室の活動について，2017年度および2018年度半ばまでの状況を報告するとともに，関連する事業内容について，考察を加える。本稿で記載する約１年半の中で，2016～2017年度にINPIT（独立行政法人工業所有権情報・研修館）によるアドバイザー派遣事業について，2018年度に１年間の継続が決まったが，基幹校のみへの支援という形となり，２年間継続していた吉備地域産学官連携知的財産活用ネットワークについては，2017年度末にて終了となった。また2018年６月に事務系の改組が行われ，従来，研究支援係の中で担当者の業務がオーバーラップしていた部分が解消され，役割分担が明確になった。事業として主なものは，FD会の開催，国内産学官連携展示会などへの学内シーズの出展，本学発の産学官連携展示会であるKMS メディカル･アークの開催などとともに，学内の知的財産管理と研究契約等の事業を所掌している。約１年半の事業を総括する中で，関連の課題についても考察する。　Here, we report the activities of the Industry-Academia Collaboration and Intellectual Property Management Section within Kawasaki Medical School, which was established from fiscal year 2016, until 2017 and middle of 2018. In addition, we will consider the relevant business contents. Within one year and a half as described in this paper, it had decided to continue the advertisement agency work by INPIT (Independent Administrative Institution Industrial Property Information and Training Center) in 2016 to 2017 for one year in fiscal year 2018. However, it became a form of support to only core school, and the network of Kibi region industry, academia and government collaboration intellectual property which had been continuing for two years ended at the end of fiscal year 2017. In addition, the administrative system was reorganized in June 2018, and the part where the work of the person in charge was overlapped in the research support officer was resolved in the past, and the role sharing became clear. The main projects include the holding of faculty development seminar, the in-campus research-seeds at domestic industry, academia and government collaborative exhibitions, the holding of KMS Medical Ark, which is an industry-academia-government collaborative exhibition from our medical school, our section manage the intellectual property and also engaged in business such as management and research contracts. While summarizing the projects for about a year and a half, related issues are also discussed

産学連携知的財産管理室 : 2018年度から2019年度半ばまでの活動報告

　川崎医科大学内の産学連携知的財産管理室（産知室）の活動について，2018年度および2019年度半ばまでの活動を報告するとともに，関連する事業内容について考察を加える。５年度目に入ったINPIT（独立行政法人工業所有権情報・研修館）によるアドバイザー派遣事業は，最終年度の2018年度は基幹校のみへの支援であった。主な事業は，Faculty Development（FD）会の開催，国内産学官連携展示会などへの学内シーズの出展，本学発の産学官連携展示会であるKMS メディカル･アークの開催とともに，学内の知的財産管理と研究契約等の整備であった。特許申請や共同研究については実績が上がり，支援してきた小児外科学教室植村教授発案の漏斗胸矯正具スタビライザーが医療機器として承認，保険収載され上市された。またKMS メディカル･アークも軌道にのり，メディカル・スタッフのニーズ提案からの製品化事案も３件が進行している。しかし今後，申請された特許案件の審査請求や，種々のシーズやニーズと企業を結び付ける調整職種の充実などの課題が表出しており検討していかなければならない。　Here, we report the activities of the Industry-Academia Collaboration and Intellectual Property Management Section (IACIPM) within Kawasaki Medical School since fiscal year (FY) 2018 until mid-2019, and consider the relevant business contents.　The advisor dispatching business by INPIT (The National Center for Industrial Property Information and Training), which entered the fifth year, was only for core schools in the final year of 2018. The main activities are holding the Faculty Development (FD) meeting, exhibiting on-campus seeds at domestic industry-academia-government collaboration exhibitions, holding KMS Medical Ark, and maintenance of property management and research contracts. The patent application and collaborating researches have been increased, and the funnel chest correction device stabilizer designed by Professor Uemura of Pediatric Surgery, which has been supported, has been approved as a medical device, put on insurance, and marketed. KMS Medical Ark is also on track, and there are three cases of commercialization based on the needs of medical staff. In the future, however, issues such as requests for examination of patent applications that have been filed and various types of coordinating jobs that link companies with various seeds and needs will be revealed and must be considered