Introduction: Although sinapic acid is found in various edible plants and has been shown to have anti-inflammatory properties including colitis, its underlying mechanism and effects on the composition of the gut microbiota are largely unknown. We aimed to identify an early response kinase that regulates the localization of tight junction proteins, act at the onset of the inflammatory response, and is regulated by sinapic acid. Additionally, we analyzed the effects of sinapic acid on the homeostasis of the intestinal microbiome. Methods: We examined the aberrant alterations of early response genes such as nuclear factor-kappa B (NF-κB) and activating transcription factor (ATF)-2 within 2 h of sinapic acid treatment in fully differentiated Caco-2 cells with or without lipopolysaccharide and tumor necrosis factor (TNF)-α stimulation. To confirm the effect of sinapic acid on stimulus-induced delocalization of tight junction proteins, including zonula occludens (ZO)-1, occludin, and claudin-2, all tight junction proteins were investigated by analyzing a fraction of membrane and cytosol proteins extracted from Caco-2 cells and mice intestines. Colitis was induced in C57BL/6 mice using 2% dextran sulfate sodium and sinapic acid (2 or 10 mg/kg/day) was administrated for 15 days. Furthermore, the nutraceutical and pharmaceutical activities of sinapic acid for treating inflammatory bowel disease (IBD) evaluated. Results: We confirmed that sinapic acid significantly suppressed the stimulus-induced delocalization of tight junction proteins from the intestinal cell membrane and abnormal intestinal permeability as well as the expression of inflammatory cytokines such as interleukin (IL)-1β and TNF-α in vitro and in vivo. Sinapic acid was found to bind directly to transforming growth factor beta-activated kinase 1 (TAK1) and inhibit the stimulus-induced activation of NF-κB as well as MAPK/ATF-2 pathways, which in turn regulated the expression of mitogen-activated protein kinase (MLCK). Dietary sinapic acid also alleviated the imbalanced of gut microbiota and symptoms of IBD, evidenced by improvements in the length and morphology of the intestine in mice with colitis. Discussion: These findings indicate that sinapic acid may be an effective nutraceutical and pharmaceutical agent for IBD treatment as it targets TAK1 and inhibits subsequent NF-κB and ATF-2 signaling.

IbMYB1 was one of the major anthocyanin biosynthesis regulatory genes that has been identified and utilized in purple-fleshed sweet potato breeding. At least three members of this gene, namely, IbMYB1-1, -2a, and -2b, have been reported. We found that IbMYB1-2a and -2b are not necessary for anthocyanin accumulation in a variety of cultivated species (hexaploid) with purple shoots or purplish rings/spots of flesh. Transcriptomic and quantitative reverse transcription PCR (RT-qPCR) analyses revealed that persistent and vigorous expression of IbMYB1 is essential to maintain the purple color of leaves and storage roots in this type of cultivated species, which did not contain IbMYB1-2 gene members. Compared with IbbHLH2, IbMYB1 is an early response gene of anthocyanin biosynthesis in sweet potato. It cannot exclude the possibility that other MYBs participate in this gene regulation networks. Twenty-two MYB-like genes were identified from 156 MYBs to be highly positively or negatively correlated with the anthocyanin content in leaves or flesh. Even so, the IbMYB1 was most coordinately expressed with anthocyanin biosynthesis genes. Differences in flanking and coding sequences confirm that IbMYB2s, the highest similarity genes of IbMYB1, are not the members of IbMYB1. This phenomenon indicates that there may be more members of IbMYB1 in sweet potato, and the genetic complementation of these members is involved in the regulation of anthocyanin biosynthesis. The 3\' flanking sequence of IbMYB1-1 is homologous to the retrotransposon sequence of TNT1-94. Transposon movement is involved in the formation of multiple members of IbMYB1. This study provides critical insights into the expression patterns of IbMYB1, which are involved in the regulation of anthocyanin biosynthesis in the leaf and storage root. Notably, our study also emphasized the presence of a multiple member of IbMYB1 for genetic improvement.

The activation of Ca2+-permeable N-methyl-D-aspartic acid (NMDA) receptor channels (NMDARs) is crucial for the development and survival of neurons, but many cancers use NMDAR-mediated signaling as well, enhancing the growth and invasiveness of tumors. Thus, NMDAR-dependent pathways emerge as a promising target in cancer therapy. Here, we use the LN229 and U-87MG glioblastoma multiforme (GBM) cells and immunofluorescence staining of 53BP1 to analyze NMDAR-induced DNA double-strand breaks (DSBs), which represent an important step in the NMDAR signaling pathway in neurons by facilitating the expression of early response genes. Our results show that NMDAR activation leads to the induction of DSBs in a subpopulation of glioma cells. In a further analogy to neurons, our results demonstrate that the induction of DSBs in LN229 cells is dependent on the activity of topoisomerase IIβ (Top2β). Western blot analysis revealed that the inhibition of NMDARs, cAMP-responsive element binding transcription factor (CREB) and Top2β decreased the expression of the proto-oncogene cFos. Knockdown of Top2β with siRNAs resulted in a downregulation of cFos and increased the radiosensitivity of LN229 cells in clonogenic survival. We also observed impaired cFos expression upon NMDAR and Top2β inhibition in a primary GBM cell line, suggesting that NMDAR signaling may be widely used by GBMs, demonstrating the potential of targeting NMDAR signaling proteins for GBM therapy.