Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis and Bioevaluation.

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides (4 a-i, 7 a-g) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI-H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a-i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a-g in all biological assays. Compounds 7 e-f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 µM and 1.794±0.159 µM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.

Spectrum-effect relationship between high-performance thin-layer chromatography data and xanthine oxidase inhibitory activity of celery seed extract.

Celery seeds are medicinal herbs used for the prevention and treatment of gout as these have the ability to inhibit the activity of xanthine oxidase and reduce the concentration of serum uric acid. In this study, the relationship between xanthine oxidase inhibitory effects and high-performance thin-layer chromatography data of celery seed extracts was established using multilayer neural network (MNN) in combination with principal component analysis (PCA). The constructed MNN-PCA model was stable and had accurate prediction ability with coefficient of determination = 0.9998, leave-one-out coefficient = 0.7371, root mean square error = 0.0025, and mean absolute deviation = 0.0019 for the training set and coefficient of determination = 0.8124, root mean square error = 0.0784, and mean absolute deviation = 0.0645 for the test set. This model can be used to identify the main compounds related to the xanthine oxidase inhibitory effect of celery seed extract. These results can be applied not only to celery extract but also to other herbal medicines.

Deep eutectic solvent combined with soybean as an efficient approach to enhance the content of apigenin in the Chrysanthemum indicum L. extract.

Our research aimed to cost-effectively enhance apigenin content in Chrysanthemum indicum L. extract using soybeans combined with a deep eutectic solvent. First, various deep eutectic solvents were investigated for the extraction of apigenin, followed by soybean treatment to increase aglycon levels. Combining single factor experiments with response surface methodology and optimization algorithms (genetic algorithm and particle swarm optimization), the optimal conditions were also determined. The results revealed that choline chloride-propylene glycol emerged as the optimal solvent. The optimized treatment conditions involved a temperature of 54 °C, a time of 2 h, and the addition of 3 mL of soybean extract, yielding an apigenin content of 3.380 ± 0.031 mg/g - a remarkable eightfold increase compared to the initial extract. The computational study suggested that the deep eutectic solvent may play an important role in stabilizing ß-glucosidase in soybeans. However, further research is needed to scale up and fully elucidate soybean's mechanism.

Negotiating agency in cases of intimate partner violence in Vietnam.

Understandings of women's agency in cases of intimate partner violence (IPV) have been dominated by an individualistic focus on help-seeking behaviour. The role of children in influencing, enabling and restricting the decision-making processes of their mothers has been largely ignored. We adopt biographical analytical approaches to qualitative longitudinal data collected as part of the Young Lives study to highlight the interdependency of women's and children's agency in contexts of IPV in Vietnam. We illustrate how women's agency is both enabled and constrained by their relationships with their children, as well as by wider structural processes, and examine how gender and generation intersect. In marginalised settings where few formal services exist or strong social norms preclude women from accessing support, understanding these informal coping strategies and the processes by which these are negotiated is essential for developing more effective policy responses.

Tbx2a is required for specification of endodermal pouches during development of the pharyngeal arches.

Tbx2 is a member of the T-box family of transcription factors essential for embryo- and organogenesis. A deficiency in the zebrafish paralogue tbx2a causes abnormalities of the pharyngeal arches in a p53-independent manner. The pharyngeal arches are formed by derivatives of all three embryonic germ layers: endodermal pouches, mesenchymal condensations and neural crest cells. While tbx2a expression is restricted to the endodermal pouches, its function is required for the normal morphogenesis of the entire pharyngeal arches. Given the similar function of Tbx1 in craniofacial development, we explored the possibility of an interaction between Tbx1 and Tbx2a. The use of bimolecular fluorescence complementation revealed the interaction between Tbx2a and Tbx1, thus providing support for the idea that functional interaction between different, co-expressed Tbx proteins could be a common theme across developmental processes in cell lineages and tissues. Together, this work provides mechanistic insight into the role of TBX2 in human disorders affecting the face and neck.