Comprehensive Study in the Inhibitory Effect of Berberine on Gene Transcription, Including TATA Box

Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box

GSK-3 Activity Is Critical for the Orientation of the Cortical Microtubules and the Dorsoventral Axis Determination in Zebrafish Embryos

The formation of dorsal-ventral (D–V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos

Effect of Freeze-Thaw Cycles on Juice Properties, Volatile Compounds and Hot-Air Drying Kinetics of Blueberry

This paper studied the effects of freeze-thaw (FT) cycles on the juice properties and aroma profiles, and the hot-air drying kinetics of frozen blueberry. After FT treatment, the juice yield increased while pH and total soluble solids of the juice keep unchanged. The total anthocyanins contents and DPPH antioxidant activities of the juice decreased by FT treatments. The electronic nose shows that FT treatments significantly change the aroma profiles of the juice. The four main volatile substances in the fresh juice are (E)-2-hexenal, α-terpineol, hexanal and linalyl formate, which account for 48.5 ± 0.1%, 17.6 ± 0.2%, 14.0 ± 1.5% and 7.8 ± 2.7% of relative proportions based on total ion chromatogram (TIC) peak areas. In the FT-treated samples, the amount of (E)-2-hexenal and hexanal decreased significantly while α-terpineol and linalyl formate remained almost unchanged. Repeated FT cycles increased the ethanol content and destroyed the original green leafy flavor. Finally, the drying kinetics of FT-treated blueberries was tested. One FT treatment can shorten the drying time by about 30% to achieve the same water content. The Deff values of the FT-treated sample are similar, which are about twice as large as the value of the fresh sample. The results will be beneficial for the processing of frozen blueberry into juice or dried fruits

Well-Defined Nanostructures by Block Copolymers and Mass Transport Applications in Energy Conversion

With the speedy progress in the research of nanomaterials, self-assembly technology has captured the high-profile interest of researchers because of its simplicity and ease of spontaneous formation of a stable ordered aggregation system. The self-assembly of block copolymers can be precisely regulated at the nanoscale to overcome the physical limits of conventional processing techniques. This bottom-up assembly strategy is simple, easy to control, and associated with high density and high order, which is of great significance for mass transportation through membrane materials. In this review, to investigate the regulation of block copolymer self-assembly structures, we systematically explored the factors that affect the self-assembly nanostructure. After discussing the formation of nanostructures of diverse block copolymers, this review highlights block copolymer-based mass transport membranes, which play the role of “energy enhancers” in concentration cells, fuel cells, and rechargeable batteries. We firmly believe that the introduction of block copolymers can facilitate the novel energy conversion to an entirely new plateau, and the research can inform a new generation of block copolymers for more promotion and improvement in new energy applications

Construction and Ion Transport-Related Applications of the Hydrogel-Based Membrane with 3D Nanochannels

Hydrogel is a type of crosslinked three-dimensional polymer network structure gel. It can swell and hold a large amount of water but does not dissolve. It is an excellent membrane material for ion transportation. As transport channels, the chemical structure of hydrogel can be regulated by molecular design, and its three-dimensional structure can be controlled according to the degree of crosslinking. In this review, our prime focus has been on ion transport-related applications based on hydrogel materials. We have briefly elaborated the origin and source of hydrogel materials and summarized the crosslinking mechanisms involved in matrix network construction and the different spatial network structures. Hydrogel structure and the remarkable performance features such as microporosity, ion carrying capability, water holding capacity, and responsiveness to stimuli such as pH, light, temperature, electricity, and magnetic field are discussed. Moreover, emphasis has been made on the application of hydrogels in water purification, energy storage, sensing, and salinity gradient energy conversion. Finally, the prospects and challenges related to hydrogel fabrication and applications are summarized

Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST

Protocadherin 15 (PCDH15) is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations of PCDH15 gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN) and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23). Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15

Sea Cucumber-Derived Peptides Alleviate Oxidative Stress in Neuroblastoma Cells and Improve Survival in <i>C. elegans</i> Exposed to Neurotoxic Paraquat.

Funder: Wellcome TrustOxidative stress results when the production of oxidants outweighs the capacity of the antioxidant defence mechanisms. This can lead to pathological conditions including cancer and neurodegeneration. Consequently, there is considerable interest in compounds with antioxidant activity, including those from natural sources. Here, we characterise the antioxidant activity of three novel peptides identified in protein hydrolysates from the sea cucumber Apostichopus japonicus. Under oxidative stress conditions, synthetic versions of the sea cucumber peptides significantly compensate for glutathione depletion, decrease mitochondrial superoxide levels, and alleviate mitophagy in human neuroblastoma cells. Moreover, orally supplied peptides improve survival of the Caenorhabditis elegans after treatment with paraquat, the latter of which leads to the production of excessive oxidative stress. Thus, the sea cucumber peptides exhibit antioxidant activity at both the cellular and organism levels and might prove attractive as nutritional supplements for healthy ageing