Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

ガッコウ ゲンバ ノ ガッコウ キンキュウ シエン ニツイテノ ヨウボウ ニ カンスル チョウサ ケンキュウ : ガッコウ キンキュウ シエン マニュアル ト キット サクセイ ニ ムケテ

学校緊急支援のためのマニュアルとキットを作成するために、学校緊急支援についての要望について秋田県内すべての教育委員会、高等学校、中学校、小学校といくつかの幼稚園・保育園に対して、自作の質問紙による調査を行った。結果、527人(回収率51.7%)から回答を得た。回答者は、教頭、養護教諭が多かった。学校緊急支援については、75.9%の回答者が知っていた。学校緊急支援を必要とする事案は多様であるが、回答者は、「校内(敷地内)」「自殺」「死傷」という事案で多く必要性を感じていた。必要とする人材は、複数の臨床心理士、教育委員会職員などであり、2～3日から1週間程度の支援を望んでいた。希望する支援内容は、カウンセリング、心理的ダメージの評価、子供への接し方についての専門的アドバイスなどであった。For the purpose of making a School Crisis Intervention (SCI) manual and a kit, data on needs for SCI for school teachers were collected from all educational boards, high schools, junior high schools, elementary schools and some nursery schools in Akita prefecture through the use of a self‑evaluating questionnaire. As a result, we received data from 527 school teachers, a return rate of 51.7%. They were mainly from assistant principals and Yogo‑Teachers (nurse‑teachers.) 75.9% of them were familiar with SCI but said they needed SCI guidance in various situations especially situations such as "in school (on campus)," "suicide," "deaths or injuries." Regarding the human resources for SCI, they would need some assistance from clinical psychologists and members of the board of education from a few days up to a week. They also would expect counseling, assessment of psychological damage and advice from specialist dealing with such affected children