Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5–20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.

One of the serious sequelae of chronic hepatitis B virus (HBV) infection is hepatocellular carcinoma (HCC). Among all the proteins encoded by the HBV genome, hepatitis B virus X protein (HBx) is highly associated with the development of HCC. Although Notch1 signaling has been found to exert a tumor-suppressive function during HCC development, the mechanism of interaction between HBx expression and Notch1 signaling needs to be explored. In this study, we report that HBx expression in hepatic and hepatoma cells resulted in decreased endogenous protein levels of Notch1 intracellular domain (ICN1) and messenger RNA levels of its downstream target genes. These effects were due to a reduction of Notch1 cleavage by HBx through the suppression of presenilin1 (Psen1) transcription rather than inhibition of Notch1 transcription or its ligands' expression. Through transient HBx expression, decreased ICN1 resulted in enhanced cell proliferation, induced G1-S cell cycle progression, and blunted cellular senescence in vitro. Furthermore, the effect of blunted senescence-like growth arrest by stable HBx expression through suppression of ICN1 was shown in a nude mouse xenograft transplantation model. The correlation of inhibited Psen1-dependent Notch1 signaling and blunted senescence-like growth arrest was also observed in HBV-associated HCC patient tumor samples. Conclusion: Our results reveal a novel function of HBx in blunting senescence-like growth arrest by decreasing Notch1 signaling, which could be a putative molecular mechanism mediating HBV-associated hepatocarcinogenesis. (HEPATOLOGY 2010;52:142-154) H epatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related death in humans, with nearly 600,000 deaths annually worldwide. 1,2 Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor for the development of HCC, especially in southeastern Asia and sub-Saharan Africa. [3][4][5] Several processes are involved in the development of HBV-associated hepatocellular carcinoma, including integration of HBV genes into host cell genome, sustained cycles of necrosis-inflammation-regeneration, activation of oncogenic pathways, and inactiAbbreviations: BrdU, 5-bromo-2 0 -deoxyuridine; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HBV, hepatitis B virus; HBx, hepatitis B virus X protein; HCC, hepatocellular carcinoma; ICN1, Notch1 intracellular domain; mRNA, messenger RNA; NEXT1, extracellular truncated Notch1; Notch1-FL, full-length Notch1; qRT-PCR, quantitative real-time polymerase chain reaction; Psen1, presenilin1; Psen2, presenilin2; SA-b-gal, senescence-associated b-galactosidase; SD, standard deviation; TACE, tumor necrosis factor-a-converting enzyme.From the

Type 2 diabetes mellitus (T2DM) is the most prevalent disease and becoming a serious public health threat worldwide. It is a severe endocrine metabolic disorder which has the ability to induce serious complications in all kinds of organs. Although the mechanisms of anti-diabetics have been described before, we focus here on the cellular and physiological mechanisms on the modulation of insulin and blood glucose. As obesity and inflammation are intimately associated with the development of T2DM, the possible relationships of them were described. We investigated and discussed the effects of gut microbiota on insulin resistance in human clinical trials and the potential mechanisms and roles whereby gut microbiota improve glucose metabolism. Phytochemicals have historically underlied their effects with therapeutic potential on T2DM, and nowadays still represent an important pool for the identification of novel drug leads. The anti-diabetic effects of natural species that are used in medicines or as nutraceuticals were described.The objective of the present study was to make a systematic review on glucose metabolism in T2DM as well as to explore the relationship between glucose metabolism and natural phytochemicals.

Helicobacter pylori α1–3/4-fucosyltransferase (Hp3/4FT) was expressed in Escherichia coli at a level of 30 mg/L culture and used as a diverse catalyst in a one-pot multienzyme (OPME) system for high-yield production of L-fucose-containing carbohydrates including Lewis antigens such as Lewis a, b, x, O-sulfated Lewis x, and sialyl Lewis x as well as human milk fucosides such as 3-fucosyllactose (3-FL), lacto-N-fucopentaose (LNFP) III, lacto-N-difuco-hexaose (LNDFH) II and III. Noticeably, while difucosylation of tetrasaccharides was readily achieved using an excess amount of donor, synthesis of LNFP III was achieved by Hp3/4FT-catalyzed selective fucosylation of the N-acetyllactoamine (LacNAc) component in lacto-N-neotetraose (LNnT).

Functional properties, structural studies and chemoenzymatic synthesis of oligosaccharides http://researchonline.ljmu.ac.uk/6683/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. The authors declare that there is no conflict of interest regarding the publication of this article. 17Abstract: Oligosaccharides offer beneficial effects on immune system and gut health, such 18 as anticancer activity, immunomodulatory activity, and complement activation.

The gastrointestinal tract of pigs is densely populated with microorganisms that closely interact with the host and with ingested feed. Gut microbiota benefits the host by providing nutrients from dietary substrates and modulating the development and function of the digestive and immune systems. An optimized gastrointestinal microbiome is crucial for pigs' health, and establishment of the microbiome in piglets is especially important for growth and disease resistance. However, the microbiome in the gastrointestinal tract of piglets is immature and easily influenced by the environment. Supplementing the microbiome of piglets with probiotic bacteria such as Lactobacillus could help create an optimized microbiome by improving the abundance and number of lactobacilli and other indigenous probiotic bacteria. Dominant indigenous probiotic bacteria could improve piglets' growth and immunity through certain cascade signal transduction pathways. The piglet body provides a permissive habitat and nutrients for bacterial colonization and growth. In return, probiotic bacteria produce prebiotics such as short-chain fatty acids and bacteriocins that benefit piglets by enhancing their growth and reducing their risk of enteric infection by pathogens. A comprehensive understanding of the interactions between piglets and members of their gut microbiota will help develop new dietary interventions that can enhance piglets' growth, protect piglets from enteric diseases caused by pathogenic bacteria, and maximize host feed utilization.

No abstract

A novel α1–2-fucosyltransferase from Thermosynechococcus elongatus BP-1 (Te2FT) with high fucosyltransferase activity and low donor hydrolysis activity was discovered and characterized. It was used in an efficient one-pot multienzyme (OPME) fucosylation system for high-yield synthesis of human blood group H antigens containing β1–3-linked galactosides and an important human milk oligosaccharide (HMOS) lacto-N-fucopentaose I (LNFP I) in preparative and gram scales. LNFP I was shown to be selectively consumed by Bifidobacterium longum subsp. infantis but not Bifidobacterium animalis subsp. lactis and is a potential prebiotic.