Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-tran...Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.展开更多
Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation re...Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation represents the satisfaction or the dissatisfaction of relationship, connection or correspondence between the objects of two or more sets. However, there are some problems that can’t be solved through classical relationships, such as the relationship between two objects being vague. In those situations, picture fuzzy relation over picture fuzzy sets is an important and powerful concept which is suitable for describing correspondences between two vague objects. It represents the strength of association of the elements of picture fuzzy sets. It plays an important role in picture fuzzy modeling, inference and control system and also has important applications in relational databases, approximate reasoning, preference modeling, medical diagnosis, etc. In this article, we define picture fuzzy relations over picture fuzzy sets, including some other fundamental definitions with illustrations. The max-min and min-max compositions of picture fuzzy relations are defined in the light of picture fuzzy sets and discussed some properties related to them. The reflexivity, symmetry and transitivity of a picture fuzzy relation are described over a picture fuzzy set. Finally, various properties are explored related to the picture fuzzy relations over a picture fuzzy set.展开更多
文摘Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.
文摘Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation represents the satisfaction or the dissatisfaction of relationship, connection or correspondence between the objects of two or more sets. However, there are some problems that can’t be solved through classical relationships, such as the relationship between two objects being vague. In those situations, picture fuzzy relation over picture fuzzy sets is an important and powerful concept which is suitable for describing correspondences between two vague objects. It represents the strength of association of the elements of picture fuzzy sets. It plays an important role in picture fuzzy modeling, inference and control system and also has important applications in relational databases, approximate reasoning, preference modeling, medical diagnosis, etc. In this article, we define picture fuzzy relations over picture fuzzy sets, including some other fundamental definitions with illustrations. The max-min and min-max compositions of picture fuzzy relations are defined in the light of picture fuzzy sets and discussed some properties related to them. The reflexivity, symmetry and transitivity of a picture fuzzy relation are described over a picture fuzzy set. Finally, various properties are explored related to the picture fuzzy relations over a picture fuzzy set.
