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Romagnoli, Romeo,Baraldi, Pier Giovanni,Lopez-Cara, Carlota,Cruz-Lopez, Olga,Carrion, Maria Dora,Kimatrai Salvador, Maria,Bermejo, Jaime,Est?vez, Sara,Est?vez, Francisco,Balzarini, Jan,Brancale, Andre Wiley-VCH 2011 CHEMMEDCHEM Vol.6 No.10
<P>Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth occurred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3',4',5'-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3 h), which inhibits cancer cell growth at nanomolar concentrations (IC(50) =16-24 nM), and interacts strongly with tubulin by binding to the colchicine site. Sub-G(1) apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3 h in a concentration-dependent manner. We also show that compound 3 h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an α-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives.</P>
Carlotta Pia Cristalli,Chiara Zannini,Giorgia Comai,Olga Baraldi,Vania Cuna,Maria Cappuccilli,Vilma Mantovani,Niccolò Natali,Giuseppe Cianciolo,Gaetano La Manna 한국유전학회 2017 Genes & Genomics Vol.39 No.7
Gene polymorphisms involved in homocysteine- methionine pathway result in hyperhomocysteinemia, a predisposing condition to several diseases. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate and homocysteine metabolism. The two known functional polymorphisms of MTHFR gene, 677C>T and 1298A>C have been implicated in a variety of multifactorial diseases: cardio-cerebrovascular and neurodegenerative disorders, autoimmune diseases, birth defects, diabetes, neuropsychiatric disorders, cancer and renal disease. C667T, and to a lesser extent A1298C polymorphisms, have been also reported to have a pharmacogenetic role in predicting drug toxicity in cancer and rheumatoid arthritis treatment. We review here the principal effects of the MTHFR gene variations in different clinical conditions.
Castiblanco Diana Maryuri Correa,Lima Michele Bernardino de,Artoni Silvana Martinez Baraldi,Raimundo Erikson Kadoshe de Morais,Santos Daniel Silva,Carvalho Lizia Cordeiro de,Silva Edney Pereira da 아세아·태평양축산학회 2023 Animal Bioscience Vol.36 No.1
Objective: Current quail production is configured as an economic activity in scale. Advancements in quail nutrition have been limited to areas such as breeding and, automation of facilities and ambience. The objective of this study was to evaluate the performance responses, liver and oviduct morphometry, and liver histology of Japanese laying quails subjected to different levels of nitrogen-corrected apparent metabolizable energy (MEn). Methods: A completely random design was used that consisted of nine levels of MEn, six replicates, and five hens per cage with a total of 270 quails. The experimental period lasted for 10 weeks. The variables of performance were subjected to analysis of variance and then regression analysis using the broken-line model. The morphometric and histological variables were subjected to multivariate exploratory techniques. Results: The MEn levels influenced the responses to zootechnical performance. The brokenline model estimated the maximum responses for feed intake, egg production, egg weight, and egg mass as 3,040, 2,820, 1,802, and 2,960 kcal of MEn per kg of diet, respectively. Multivariate analysis revealed that the occurrence of hepatic steatosis and increased levels of Kupffer cells were not related to MEn levels. Conclusion: The level of 2,960 kcal/kg of MEn meets performance variable requirements without compromising hepatic physiology.