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        Glycyrrhetic acid monoglucuronide: sweetness concentration–response and molecular mechanism as a naturally high-potency sweetener

        Yongan Yang,Yuangang Wei,Xiaonan Guo,Pengfei Qi,Hailiang Zhu,Wenjian Tang 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.4

        Glycyrrhetic acid monoglucuronide (GAM) isobtained from the natural sweetener glycyrrhizin throughenzymolysis. Its sweetness concentration–response (C–R)behavior in room-temperature in water was determinedusing two-alternative forced choice discrimination tests. The C–R equation of resultant hyperbolic curve relatingsucrose equivalent (SE, %) to GAM concentration([GAM], mg/L) was SE = 19.6 9 [GAM]/(194.8 ? [GAM]). From the C–R function, Pw (2) ofGAM, relative to a 2% (w/v) sucrose reference, is morethan 900, which has much higher potency than its precursorglycyrrhizin. Molecular modeling showed that GAM isfinely bound into protein 1EWK through conventionalhydrogen bonds, p-Alkyl interactions and Van der Waalsbonds, which exhibited better protein inclusion than Glycyrrhizin. Thus, GAM could be developed

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        Effects of Flammulina velutipes polysaccharides on gut microbiota composition and metabolism in vitro fermentation

        Anxiang Su,Gaoxing Ma,Ning Ma,Fei Pei,Wenjian Yang,Qiuhui Hu 한국식품과학회 2023 Food Science and Biotechnology Vol.32 No.3

        Flammulina velutipes polysaccharides (FVP) exhibit many biological activities, but the effects on gut microflora and metabolism were still unclear. Here, we explored the composition of FVP, their influence on human gut microflora composition and metabolites. FVP were used to vitro fermentation through human fecal inoculums. In addition, 16S rRNA sequencing were used to assess the effects of FVP on the gut microbiota. The metabolic profiles were investigated using untargeted metabolomics approaches in the LC-MS platform. The results showed that FVP was mainly consisted of glucose, mannose, xylose, fucose and galactose. FVP is shown to increase the relative abundances of Bifidobacteriaceae, as well as Bacteroidaceae and remarkably decrease the numbers of genera Lachnospiraceae coupled with Enterococcaceae. The differential metabolites were identified and mainly involved the metabolism of glycerophospholipid, linoleic acid and synthesis of unsaturated fatty acids. FVP may exhibit biological activity function by regulating gut microflora composition and metabolites.

      • Hippo signaling is intrinsically regulated during cell cycle progression by APC/C<sup>Cdh1</sup>

        Kim, Wantae,Cho, Yong Suk,Wang, Xiaohui,Park, Ogyi,Ma, Xueyan,Kim, Hanjun,Gan, Wenjian,Jho, Eek-hoon,Cha, Boksik,Jeung, Yun-ji,Zhang, Lei,Gao, Bin,Wei, Wenyi,Jiang, Jin,Chung, Kyung-Sook,Yang, Yingzi National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.19

        <P><B>Significance</B></P><P>The Hippo signaling pathway is evolutionarily conserved in the animal kingdom and plays essential roles in regulating tissue growth during development and regeneration. We have identified APC/C<SUP>Cdh1</SUP>, a core component of cell cycle control machinery, as an evolutionarily conserved and previously unknown regulator of large tumor suppressor (LATS) kinases, which critically inhibit the YAP/TAZ transcription factors in transducing Hippo signaling. Our results suggest a model that APC/C<SUP>Cdh1</SUP> destabilizes LATS1/2 kinases in G1 phase of the cell cycle, leading to increased YAP/TAZ activities that promote G1/S transition by upregulating downstream gene expression, including <I>E2F1</I>. Our findings have important implications for a link between cell proliferation and LATS-regulated YAP/TAZ activities.</P><P>The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)<SUP>Cdh1</SUP> E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in <I>Drosophila</I> eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C<SUP>Cdh1</SUP> represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.</P>

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