Angelica sinensis and Its Alkylphthalides Induce the Detoxification Enzyme NAD(P)H: Quinone Oxidoreductase 1 by Alkylating Keap1

The roots of Angelica sinensis (Oliv.) Diels (Dang Gui; Apiaceae) have a long history in traditional Chinese medicine as a remedy for women’s disorders and are often called “lady’s ginseng”. Currently, extracts of A. sinensis are commonly included in numerous dietary supplements used for women’s health and as antiaging products. In the present study, we examined the potential chemopreventive activity of A. sinensis extracts by measuring the relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). The lipophilic partitions showed strong NQO1 induction with concentrations to double the enzyme activity (CD) of 5.5 ± 0.7 (petroleum ether) and 3.9 ± 0.5 μg/mL (chloroform). Fractionation led to the isolation of phenolic esters and alkylphthalides, especially Z-ligustilide, the main lipophilic compound, which showed strong NQO1 inducing properties (CD = 6.9 ± 1.9 μM). Transcription of many detoxifying enzymes is regulated through the antioxidant response element (ARE) and its transcription factor Nrf2, which is repressed under basal conditions by Keap1. However, exposure to electrophilic inducers that alkylate Keap1 results in higher concentrations of free Nrf2 and ARE activation. The ARE reporter activity was therefore analyzed in HepG2-ARE-C8 cells after incubation with lipophilic extracts of A. sinensis or ligustilide for 24 h. Under these conditions, both the extract and the ligustilide increased ARE-luciferase reporter activity in a dose-dependent manner. Incubation of ligustilide with GSH and subsequent LC-MS-MS analysis revealed that ligustilide as well as oxidized ligustilide species covalently modified GSH. In addition, using MALDI-TOF mass spectrometry and LC-MS-MS, it was demonstrated that the lipophilic extracts, ligustilide, and monooxygenated ligustilide alkylated important cysteine residues in human Keap1 protein, thus activating Nrf2 and transcription of ARE regulated genes. These observations suggest that A. sinensis dietary supplements standardized to ligustilide have potential as chemopreventive agents through induction of detoxification enzymes

Concert de l'Orquestra Filharmònica de Leningrad, director Evgeni Miravinski

Es van interpretar: Romeu i Julieta (segona suite) de Prokofiev i la Simfonia núm. 5 en mi menor, op. 64 de Txaikovsk

Concert de l'Orquestra Filharmònica de Leningrad, director Peeter Lilie

Es van interpretar: Simfonia núm. 82 en do major, L'ós de Haydn, Concert núm. 1 en re major, per a violí i orquestra, op. 19 de Prokofiev, Simfonia núm. 6 en si menor, op. 74, Patètica, de Txaikovsk

I Festival de ópera

Programa del primer Festival d'òpera del Patronat Pro musica de Barcelona, que es va celebrar del 28 de maig al 5 de juny de 1981 i durant el qual es va presentar la companyia del Teatre Kirov de Leningrad. En primer lloc es va representar "Eugene Oneguin" de P. I. Txaikovski, en segon lloc es va poder veure "Boris Godunov" de M. Musorgski i la tercera obra representada fou "La dama de piques". Aquestes es van dur a terme amb els cantants E. Kraiúshkina, L. Sevchenko, O. Stronskáia, E. Gorojóvskaia, T. Kuznetsova, S. Leiferkus, V. Liebed, Z. Plúzhnikov, A. Stieblianko, N. Ojótnikov, V. Belienko, M. Chernozhúkov i V. Solodóvnikov. en la qual van actuar B. Shtókolov, V. Kiniáev, E. Parfénova, L. Diadkova, T. Nóvikova i R. Medviédeva, entre altres. Finalment es va fer un concert amb l'Orquestra Simfònica i el Cor del Teatre Kirov amb la mezzo-soprano E. Gorojovskaia en què es va interpretar la "Simfonia núm. 5 en re menor, Op. 47" de D. Shostakovich i "Alexander Nevsky, Op. 78", de S. Prokofiev. En tots els casos el director va ser Y. TemirkanovOrquestra simfònica del Teatre Kirov (actual Mariinsky) dirigida per Y. TemirkanovDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial

Dermatology-oncolog

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors