Baicalin-aluminum alleviates necrotic enteritis in broiler chickens by inhibiting virulence factors expression of Clostridium perfringens

Clostridium perfringens type A is the main cause of necrotic enteritis (NE) in chickens. Since the use of antibiotics in feed is withdrawn, it is imperative to find out suitable alternatives to control NE. Baicalin-aluminum complex is synthesized from baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi. The present study investigated the effects of baicalin-aluminum on the virulence-associated traits and virulence genes expression of C. perfringens CVCC2030, it also evaluated the in vivo therapeutic effect on NE. The results showed that baicalin-aluminum inhibited bacterial hemolytic activity, diminished biofilm formation, attenuated cytotoxicity to Caco-2 cells, downregulated the expression of genes encoding for clostridial toxins and extracellular enzymes such as alpha toxin (CPA), perfringolysin O (PFO), collagenase (ColA), and sialidases (NanI, NanJ). Additionally, baicalin-aluminum was found to negatively regulate the expression of genes involved in quorum sensing (QS) communication, including genes of Agr QS system (agrB, agrD) and genes of VirS/R two-component regulatory system (virS, virR). In vivo experiments, baicalin-aluminum lightened the intestinal lesions and histological damage, it inhibited pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) expression in the jejunal and ileal tissues. Besides, baicalin-aluminum alleviated the upregulation of C. perfringens and Escherichia coli and raised the relative abundance of Lactobacillus in the ileal digesta. This study suggests that baicalin-aluminum may be a potential candidate against C. perfringens infection by inhibiting the virulence-associated traits and virulence genes expression

Responses of the earthworm Eisenia andrei exposed to sublethal aluminium levels in an artificial soil substrate

International audienceIndustrial discharges of Al are increasingly common. In this study, the activities of three antioxidases, malondialdehyde (MDA) content and changes in coelomocytes were investigated in earthworms (Eisenia andrei) exposed to different concentrations of aluminium chloride (range 0–200 mgAl kg−1 dry soil) in artificial soils for 32 days.Within the first 16 days of Al exposure, catalase activity was elevated in most treatments, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were inhibited in all treatments. After 16 days exposure, SOD and GSH-Px activities returned to normal at lower Al concentrations, but were still inhibited at higher concentrations, hence the inhibition of SOD and GSH-Px showed some exposure-level dependence during the late exposure phase.MDAcontentwas significantly elevated from 16 days after initial exposure. Neutral Red retention time of coelomocytes decreased at the highest exposure concentrations after 32 days, and an increased proportion of cells showing membrane damagewas also observed at this time using flowcytometry.We conclude that excessive Al in soils can cause oxidative stress and cell damage in earthworms. Hence, Al accumulation in the environment may present an ecological hazard through suppression of the important functions of earthworms in soil ecosystems

Inhibition of EGFR/PI3K/AKT cell survival pathway promotes TSA\u27s effect on cell death and migration in human ovarian cancer cells

Trichostatin A (TSA), a hydroxamate-type inhibitor of mammalian histone deacetylases, is emerging as one of a potentially new class of anticancer agents. TSA is known to act by promoting the acetylation of histones, leading to uncoiling of chromatin and activation of a variety of genes implicated in the regulation of cell survival, proliferation, differentiation, and apoptosis. In addition, there is an increasing appreciation of the fact that TSA may act through mechanisms other than induction of histone acetylation. Accumulated experimental data indicate that TSA activates phosphatidyl inositol-3-kinase (PI3K)/AKT signaling. Using human ovarian cancer cell line Caov3 cells, we observed that TSA induced cell death in a time- and dose-dependent manner and also inhibited cell migration. TSA transiently activated EGFR tyrosine phosphorylation and AKT activation in a time- and dose-dependent manner, which had been inhibited by EGFR inhibitor PD153035 and PI3 kinase inhibitor LY294002. We also observed that TSA transiently induced survivin expression that had been inhibited by PD153035 and LY294002, suggesting that TSA-induced survivin expression is mediated by EGFR/PI3 kinase pathway. Combination of EGFR inhibitor 153035 or PI3 kinase inhibitor LY294002 with TSA enhanced TSA-induced cell death and TSA reduction of cell migration. Collectively, our data demonstrate that TSA transiently activated EGFR/PI3K/AKT cell survival pathway, leading to expression of survivin. Inhibition of this pathway enhanced TSA-induced cell death and inhibited cell migration. Our data suggest that combination of EGFR/PI3K/AKT cell survival pathway inhibitors with TSA be a better approach to ovarian cancer treatment

Autophagy and tight junction proteins in the intestine and intestinal diseases

The intestinal epithelium (IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus) and antigens. The apical intercellular tight junctions (TJ) are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD), necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism) is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy)-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6, interleukin-13, and interleukin-17) whose levels are increased in IBD patients cause an increase in claudin-2 expression and a claudin-2-dependent increase in TJ permeability. Thus, the role of claudin-2 in intestinal pathological processes has been attributed, in part, to the increase of intestinal TJ permeability. Claudin-2 represents a new therapeutic target in treating IBD, diarrhea and malnutrition in animals and humans. Keywords: Autophagy, Claudins, IBD, Intestinal diseases, Proinflammatory cytokines, Tight junction barrie

Antioxidant and behavior responses of earthworms after introduction to a simulated vermifilter environment

International audienceVermifiltration is a new technology for treating wastewater with a high organic loading, but there is almost no published information on the biochemical and behavioral response of earthworms in a vermifilter environment. This study measured antioxidase enzyme (AOE) activities and reactive oxygen species (ROS) and malondialdehyde (MDA) levels in tissues of earthworms for a period of 56 d after transfer into simulated vermifilters. Three vermifilter media were tested. In general AOE activities, ROS and MDA were elevated for the first 3-5 d after transfer, variable for approximately the next 7 d, and statistically indistinguishable from controls after 15 d. Similarly, earthworm activity as measured by daily burrowing length was initially enhanced but converged with that of controls after 6 d. Removal of chemical oxygen demand (COD) from artificial wastewater was significantly correlated with AOE and ROS in earthworm tissues, and daily burrowing length of earthworms, but none of these parameters was correlated to NH4+-N removal rate, suggesting earthworms do not play a direct role in nitrogen removal in vermifilters. The data provide useful information for vermifilter operators about the biochemical adaptive process earthworms undergo when introduced to a vermifilter environment and the lag time between set up and reliable operation of a vermifilter. The results could potentially lead to development of preconditioning treatments to shorten the settling-down time for newly set up vermifilters. Maximum burrow depth was reduced in simulated vermifilters, suggesting an optimal depth for vermifilter substrates. The three vermifilter media tested differed in performance and possible reasons are briefly discussed. (C) 2015 Elsevier B.V. All rights reserved

2,4-Dinitrotoluene (DNT) Perturbs Yolk Absorption, Liver Development and Lipid Metabolism/Oxygen Transport Gene Expression in Zebrafish Embryos and Larvae

2,4-dinitrotoluene (2,4-DNT) is a common environmental pollutant, and was classified as a group 2B human carcinogenic compound by the International Agency for Research on Cancer. This study determined the toxic effects of 2,4-DNT exposure on zebrafish at the embryo-larvae stage, in terms of organ morphogenesis and the expression pattern of selected target genes related to lipid metabolism and oxygen transportation. The results showed that the 120-h post-fertilization LC50 of 2,4-DNT was 9.59 mg/L with a 95% confidence interval of 8.89–10.44 mg/L. The larvae treated with 2,4-DNT showed toxic symptoms including smaller body, less skin pigment production, yolk malabsorption, and disordered liver development. Further studies on the expression of genes related to lipid transport and metabolism, and respiration indicated that they were significantly affected by 2,4-DNT. It is concluded that 2,4-DNT exposure perturbed liver development and yolk absorption in early-life zebrafish, and disturbed the lipid metabolism /oxygen transport gene expression

Treatment Effect of Multilayer Vermifiltration on Living Wastewater

International audienceFormer studies and application of vermifiltration process to organic wastewater treatment has given an affirmative effect for the pollutant removal in wastewater. It could be used for the disperse wastewater treatment, especially for rural living sewage. We developed a new multilayer vermifiltration system in this study, expecting to enhance this ability for the disposal of rural living sewage. The result showed that all the COD, BOD5 and SS values in outflow after vermifiltration could meet GB18918-2002. The removal rates of COD，BOD5 and SS were above 75%, 85% and 90% respectively. The N and P could be partly removed. These preliminary results give a positive prospective for the application of multilayer vermifiltration in rural sewage treatment in the future