Production of new amilorides as potent inhibitors of mitochondrial respiratory complex I

<div><p>Amilorides, well-known inhibitors of Na⁺/H⁺ antiporters, have also shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex I). Since the membrane subunits ND2, ND4, and ND5 of bovine mitochondrial complex I are homologous to Na⁺/H⁺ antiporters, amilorides have been thought to bind to any or all of the antiporter-like subunits; however, there is no direct experimental evidence in support of this notion. Photoaffinity labeling is a powerful technique to identify the binding site of amilorides in bovine complex I. Commercially available amilorides such as 5-(<i>N</i>-ethyl-<i>N</i>-isopropyl)amiloride are not suitable as design templates to synthesize photoreactive amilorides because of their low binding affinities to bovine complex I. Thereby, we attempted to modify the structures of commercially available amilorides in order to obtain more potent derivatives. We successfully produced two photoreactive amilorides (PRA1 and PRA2) with a photolabile azido group at opposite ends of the molecule.</p></div

Production of new amilorides as potent inhibitors of mitochondrial respiratory complex I

<div><p>Amilorides, well-known inhibitors of Na⁺/H⁺ antiporters, have also shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex I). Since the membrane subunits ND2, ND4, and ND5 of bovine mitochondrial complex I are homologous to Na⁺/H⁺ antiporters, amilorides have been thought to bind to any or all of the antiporter-like subunits; however, there is no direct experimental evidence in support of this notion. Photoaffinity labeling is a powerful technique to identify the binding site of amilorides in bovine complex I. Commercially available amilorides such as 5-(<i>N</i>-ethyl-<i>N</i>-isopropyl)amiloride are not suitable as design templates to synthesize photoreactive amilorides because of their low binding affinities to bovine complex I. Thereby, we attempted to modify the structures of commercially available amilorides in order to obtain more potent derivatives. We successfully produced two photoreactive amilorides (PRA1 and PRA2) with a photolabile azido group at opposite ends of the molecule.</p></div

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair

Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping

妖怪をテーマとする描画の試み

本研究の目的は，描画のテーマとして妖怪を用いることの効果を検討し，妖怪をテーマとする描画法の具体的な方法について考察すること であった。描画のテーマを「妖怪」とする群（妖怪群）16名と，「家にあるもの」とする群（対照群）15名を対象に，15個の刺激図形の中か ら好きな図形を模写して描き足す方法での描画を求め，描画前後の気分調査と描画後に印象評定と描画体験についてのインタビューを実施 し，描画体験の取り組みやすさや描画体験による気分の変化の違いを検討した。その結果，描画前後の気分変化について両群に共通する変化 が見られ，描画体験自体が気分を落ち着かせる可能性が示唆された。描画体験についてのインタビューでは，妖怪群のほうが満足感を得た人 が多かった。また，妖怪群は1 週間後に再インタビューを行い，妖怪への言葉がけや印象の変化を検討した。その結果，時間を置くことで親 密度の深まりや自己洞察に関する語りが見られた。これらの結果から，妖怪をテーマとする描画は侵襲性が少ないことや洞察につながること が示唆された。This study examined the effects of drawing yōkai using mixed methods. There were 16 participants in the experimental group, drawing “yōkai,” and 15 participants in the control group drawing “things at home.” All participants chose and decorated their favorite images to draw from 15 stimulus figures. To examine the differences in difficulty levels of drawing experiences and associated changes in emotions, a mood survey was administered before and after the drawing activity. An impression rating about their pictures and interview about the experience were also conducted afterwards. The results showed similar changes in mood pre- and post-activity in both groups, suggesting that the drawing activity itself may be calming. Members of the experimental group reported satisfaction more frequently than those in the control group. The experimental group was re-interviewed one week later to assess changes in their impressions regarding and (imagined) dialogue with the yōkai. Their narratives indicated deeper intimacy and self-insight, suggesting that the yōkai drawing method is a less-invasive way to promote insight