Terpenoids from Ligularia virgaurea collected in China: the first example of two bakkane derivatives with an anhydride-type ring C and nineteen new chemical constituents

Further chemical investigation of two Ligularia virgaurea samples collected in China resulted in the isolation of 21 new compounds, two of which were bakkane-type sesquiterpenoids bearing an anhydride-type ring C, which was a previously unknown partial structure. These samples belonged to the V-type (the major component was virgaurenone) among the five chemotypes found in this species

Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs

A polar liquid zwitterion does not critically destruct cytochrome c at high concentration: an initial comparative study with a polar ionic liquid

金沢大学理工研究域生命理工学系A polar carboxylate-type zwitterion with a small volume of water can dissolve cytochrome c without significant disruption, compared with the case of a popular polar carboxylate-type ionic liquid, 1-ethyl-3-methylimidazolium acetate. A change in the Soret, Q, and 615 nm bands was not observed in the 80 wt-% polar zwitterion solution, whereas a shift in the Soret band, diminishing Q band, and appearance of the 615 nm band was found in the 80 wt-% polar ionic liquid solution. It suggests that concentrated polar ionic liquid solutions critically disrupt the structure of cytochrome c, and the polar zwitterion solution used in this study was better than a 1-ethyl-3-methylimidazolium acetate solution in a high concentration range.This paper has supplementary information

Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus

Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer

津波啓発サインのデザインプロセス ―西宮市における防災意識育成のために―

西宮市災害対策課との官学連携で，武庫川女子大学生活環境学科黒田研究室所属学生8名と有志の学生7名で取り組んだ「津波啓発サイン」のデザインプロセスを報告している。このサイ ンは，450mm角のキューブを5段に積んだ立体サインである。東日本大震災の津波被害を教訓とし，南海トラフ地震が起こった場合，それに伴う津波に備えて，市民の防災意識を喚起し高めていく(啓発する)ことを目的する。大学側は，完全なボラン ティアという立場で取り組んだ。2012年11月，ワークショップという形式で開始し，2013年2月，武庫川女子大学案を西宮市に提出した。しかしながら，それを受けて西宮市が作成した案に，サインとして，情報提供の観点から問題がみられた。そのため，年度を超えて大学側が 継続的に関わることになった。研究室では，問題がみられる理由として，立体であるにもかかわらず，立体としての検討が十分ではないことが原因ではないかと考えた。そこで，西宮市案の原寸模型を作製し，問題解決の方向を検討した。さらに，原寸模型で大学案を作成し，2013年9月に大学側の最終案を西宮市に提出した。ほぼ，最終案にそうデザインで，2014年3月，立体サインが設置された

Direct preparation of gels from herbal medicinal plants by using a low toxicity liquid zwitterion

金沢大学理工研究域生命理工学系Gels containing medicinal ingredients of licorice were formed by dissolving into a biocompatible zwitterionic cellulose solvent and successive precipitation. The licorice gels gradually released glycyrrhizic acid, the main medicinal ingredient of licorice, within 3 h. Although the licorice gels were mechanically weak, gel strength was improved just by adding cellulose during the preparation of the gels.Embargo Period 6 monthsThis paper has supplementary information

Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in vivo assessment of cell to plasma ratio of miR-92a

<p>Abstract</p> <p>Background</p> <p>Plasma microRNA (miRNA) has become a promising biomarker for detecting cancer; however, it remains uncertain whether miRNA expression levels in plasma reflect those in tumor cells. Our aim was to determine the biological relevance of miR-92a, which has been implicated as an oncomiR in both plasma and leukemia cells in patients with acute leukemia and to evaluate whether it could be a novel biomarker for monitoring these patients.</p> <p>Results</p> <p>We quantified the expression level of miR-92a in both cells and plasma by reverse transcription polymerase chain reaction in 91 patients with acute leukemia. We also determined miR-92a expression levels in peripheral blood mononuclear cells (PBMNC) from normal controls. We compared miR-92a expression in plasma with its expression in leukemia cells. Synthetic anti-miR-92a inhibitor was transfected into Raji and OM9;22 cells, and apoptosis was assessed. For in vivo assessment, 6-week-old female nude mice were injected with U937 cells, and miR-92a expression in plasma and tumors was measured. The level of miR-92a expression in fresh leukemia cells was highly variable compared with PBMNC, but significantly lower compared with CD34-positive cells obtained from healthy volunteers. We also noticed that miR-92a was preferentially expressed in acute lymphoblastic leukemia (ALL) cells in comparison with acute myeloid leukemia (AML) cells. More specifically, cellular miR-92a expression was significantly increased in a subset of ALL cells, and ALL patients with overexpressed miR-92a had poor prognoses. The anti-miR-92a inhibitor-treated Raji and OM9;22 cells revealed an increase of apoptotic cells. Notably, the cell to plasma ratio of miR-92a expression was significantly higher in both AML and ALL cells compared with PBMNC from healthy volunteers. In tumor-bearing mice, the plasma miR-92a level was significantly decreased in accordance with tumor growth, while tumor tissue was strongly positive for miR-92a.</p> <p>Conclusions</p> <p>The miR-92a expression in leukemia cells could be a prognostic factor in ALL patients. The inverse correlation of miR-92a expression between cells and plasma and the cell to plasma ratio may be important to understanding the clinical and biological relevance of miR-92a in acute leukemia.</p

Cell Wall Trapping of Autocrine Peptides for Human G-Protein-Coupled Receptors on the Yeast Cell Surface

G-protein-coupled receptors (GPCRs) regulate a wide variety of physiological processes and are important pharmaceutical targets for drug discovery. Here, we describe a unique concept based on yeast cell-surface display technology to selectively track eligible peptides with agonistic activity for human GPCRs (Cell Wall Trapping of Autocrine Peptides (CWTrAP) strategy). In our strategy, individual recombinant yeast cells are able to report autocrine-positive activity for human GPCRs by expressing a candidate peptide fused to an anchoring motif. Following expression and activation, yeast cells trap autocrine peptides onto their cell walls. Because captured peptides are incapable of diffusion, they have no impact on surrounding yeast cells that express the target human GPCR and non-signaling peptides. Therefore, individual yeast cells can assemble the autonomous signaling complex and allow single-cell screening of a yeast population. Our strategy may be applied to identify eligible peptides with agonistic activity for target human GPCRs

Substrate Dependence in Aqueous Diels-Alder Reactions of Cyclohexadiene Derivatives with 1,4-Benzoquinone

Abstract: A reactivity difference based on the position of substituents on cyclohexa-1,3diene was observed for the title reaction. The effect of water as solvent was more distinct for 1-methyl-4-isopropylcyclohexa-1,3-diene than for 2-methyl-5-isopropylcyclohexa-1,3-diene or non-substituted cyclohexa-1,3-diene. The effect of NaCl (salting-out) and guanidium chloride (salting-in) was also large for 1-methyl-4-isopropylcyclohexa-1,3diene