RESUMO
From the deep sea-derived Streptomyces xiamenensis MCCC 1A01570, eight cyclic dipeptides (1-8) and five phenolics (9-13) were obtained. Cyclo-(I-Pro-D-Leu) (4) could moderately promote the gene transcriptional function of nuclear receptor RXRα, while 2, 3, and 13 showed weak reduction in RXRα gene transcriptional activities induced by 9-cis-retinoid acid (RA). These compounds might have beneficial effects against intractable diseases with relation to RXRα, such as cancer and metabolic diseases, due to their potential activities on regulating the transcriptional activation function of RXRα. In addition, 1-6, 8, 10, and 12 (20 µM) showed mild in vitro cytotoxicity against three cancer cell lines of ECA-109, Hela-S3 and PANC-1 with the inhibition rates arranging from 50% to 65%.
Assuntos
Antineoplásicos/farmacologia , Receptor X Retinoide alfa/genética , Streptomyces/química , Alitretinoína/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Dipeptídeos/química , Dipeptídeos/farmacologia , Regulação da Expressão Gênica , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenóis/química , Fenóis/farmacologia , Receptor X Retinoide alfa/metabolismo , Metabolismo Secundário , Streptomyces/isolamento & purificação , Streptomyces/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
Four new (penigrisacids A-D, 1-4) and one known (5) carotane sesquiterpenoids were isolated from the deep-sea-derived fungus Penicillium griseofulvum, along with four known compounds (6-9). The planar structures and relative configurations of the new compounds were determined by extensive analysis of the NMR and HRESIMS data. The absolute configurations were established by comparison of the experimental and calculated ECD (electronic circular dichroism) spectra or OR (optical rotation) value. Compound 9 exhibited potent anti-food allergic activity with IC50 value of 28.7 µM, while 4 showed weak cytotoxicity against ECA-109 tumor cells (IC50 = 28.7 µM).
Assuntos
Organismos Aquáticos/química , Penicillium/química , Sesquiterpenos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética/métodos , Oceanos e Mares , Sesquiterpenos/farmacologiaRESUMO
Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.
Assuntos
4-Butirolactona/análogos & derivados , Anafilaxia/tratamento farmacológico , Aspergillus/química , Hipersensibilidade Alimentar/tratamento farmacológico , Mastócitos/imunologia , 4-Butirolactona/administração & dosagem , Anafilaxia/genética , Anafilaxia/imunologia , Animais , Aspergillus/genética , Aspergillus/isolamento & purificação , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Água do Mar/microbiologiaRESUMO
Our 3-year experience with the left ventricular assist device (LVAD) research in Beijing, China, is based on experimental studies in both sheep and goats. Although testing is still in the preliminary stages, the LVAD has been implanted in seven animals, and results have been encouraging. Our most recent animal model (a goat) survived 11 days and 23 hours before succumbing to a renal embolism. The efforts described here provide a firm basis for the future of partial and total artificial heart research in our institutions.