A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice

Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes. Details of the effects of RUNX1 on the acquisition of malignancy in glioblastoma remain unclear. Here, we show that RUNX1 downregulates p21 by enhancing expressions of BIRC5 and PIF1, conferring anti-apoptotic properties on glioblastoma. A gene switch-off therapy using alkylating agent-conjugated pyrrole-imidazole polyamides, designed to fit the RUNX1 DNA groove, decreased expression levels of BIRC5 and PIF1 and induced apoptosis and cell cycle arrest via p21. The RUNX1-BIRC5/PIF1-p21 pathway appears to reflect refractory characteristics of glioblastoma and thus holds promise as a therapeutic target. RUNX gene switch-off therapy may represent a novel treatment for glioblastoma

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

医薬保健研究域薬学系The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market. Copyright © 2018 by The American Society of Tropical Medicine and Hygiene

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EDTAキレート化合物の理論的研究[安島,三次] 種々のパーフルオロカーボン陽イオンの構造と反応性 [古屋] エネルギー変換と分子認識に関する計算超分子化学の展開[杉本] Elongation method for large systems[Gu,Makowski,Korchowiec,青木] ポリフェノールデンドリマーの化学発光特性及び計算化学による分子構造解析[中園,阿川,南部,財津] 非経験的分子軌道法に基づくN-ドメイン特異的ACE阻害ペプチドの理論的予測とその評価[浦崎,益田] 非経験的分子軌道法による活性アルキル基の反応性の検討Ⅸ溶媒効果を考慮したAljyl NitriteによるIsovalerophenoneのニトロソ化反応機構[池田

Interaction Energy Analysis for Drug-Cyclodextrin Inclusion Complexes in Aqueous Solutions

It is vital to elucidate the role of asymmetric intermolecular interactions resulting from the stereospecific structures of molecules in order to understand the mechanisms of chemical and biochemical reactions such as enzyme-substrate reactions, antigen-antibody reactions, etc. In order to reveal the mechanism of the inclusion phenomenon for b-cyclodextrin (CD)-ampicillin complexes and b-CD-ibuprofen complexes, binding free energies were determined using molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) analysis. To clarify the details of the interaction energies of these complexes, pair interaction energy decomposition analysis (PIEDA) was carried out. The direction of inclusion of drugs into b-CD cavities was clarified on the basis of results obtained using the above-mentioned methods

実証的研究の事前登録の現状と実践 —OSF事前登録チュートリアル—

In the midst of the current reproducibility crisis in psychology, pre-registration is considered a remedy to increase the reliability of psychological research. However, as pre-registration is an unconventional practice for most psychological researchers, they find it difficult to introduce pre-registration into their studies. In order to promote pre-registration, this article provides a detailed and practical step-by-step tutorial for beginners on pre-registration with the Open Science Framework. Furthermore, a typical example of the practical experience of beginners and its revisions are provided as supplementary material. Finally, we discuss various issues related to pre-registration, such as transparent research, registered reports, preprints, and open science education. We hope that this article will contribute to the improvement of reproducible psychological science in Japan