Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are ...pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P<0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P<0.05). The white blood cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased significantly in heat-stressed pigs (P<0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P<0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.
We explored the mechanism by which miR-139 modulates radioresistance of esophageal cancer (EC). The radioresistant cell line KYSE150R was obtained from the parental KYSE150 cell line by fractionated ...irradiation (15×2 Gy; total dose of 30 Gy). The cell cycle was assessed by flow cytometry. A gene profiling study was conducted to detect the expression of genes related to the radioresistance of EC. In the KYSE150R line, flow cytometry revealed increased number of G1-phase cells and decreased number of G2-phase cells; the expression of miR-139 increased. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. Western blotting showed that miR-139 knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. However, PDK1 inhibitor GSK2334470 reversed this effect for p-AKT and cyclin D1 expression. A luciferase reporter assay indicated that miR-139 directly bound to the
PDK1
mRNA 3’-UTR. Analysis of the clinical data from 110 patients with EC showed an association of miR-139 expression with the TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival. In conclusion, miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.
Abstract
This study aimed to evaluate the effects of vitamin C and vitamin E on antioxidant capacity and immune function in oxidative-stressed breeder roosters. One hundred twenty 45-week-old Lveyang ...black-boned breeder roosters were randomly assigned to 5 dietary treatments, including negative control group (NC), positive control group (PC), and 3 trial groups, which were fed the diets containing 300 mg/kg VC, 200 mg/kg VE, or 300 mg/kg VC and 200 mg/kg VE (VC+VE). At 47 wk of age, the positive control and trial groups were subcutaneously injected 3 times every other d with dexamethasone (DEX) 4 mg/kg of body weight, the negative control group was injected with saline. The experiment lasted for 35 d. The results showed that at 50 wk of age, average daily feed intake of birds challenged with DEX significantly increased (P < 0.05). During post-stress recovery period (52 wk of age), dietary supplemental VE or VC+VE notably increased body weight under oxidative stress (P < 0.01). Oxidative stress induced by DEX could significantly decrease superoxide dismutase (SOD), IgM, antibody titer of ND and mRNA expression of SOD or glutathion peroxidase activity (GSH-Px), increase serous malondialdehyde (MDA) (P < 0.05). Supplementation of VC or VE significantly decreased serous MDA, and increased SOD under oxidative stress (P < 0.05). Supplementation of VC or VE, or their combination significantly increased the relative expression of GSH-Px mRNA when compared to the oxidative-stressed control treatment (P < 0.05), whereas did not alleviate the relative expression of SOD mRNA (P > 0.05). Therefore, the results suggest that addition of 300 mg/kg VC, 200 mg/kg VE or their combination could improve antioxidant ability and immune performance in oxidative-stressed breeder roosters through up-regulating the expression of GSH-Px gene.
Nanotechnology has provided many promising nanoplatforms for targeted cancer imaging and therapy. Among these platforms, gold nanoparticles (GNPs) play a unique role in medicine because of their ...excellent physical and chemical properties. To expand the applications of GNPs in medicine, amounts of targeting moieties, imaging labels, and therapeutic agents have been integrated into these particles to form multifunctionalized GNPs. In this review, we highlight recent advances of the fabrication of cancer-targeting multifunctionalized GNPs and their applications in imaging and therapy.
The pathogenicity of avian H5N1 influenza viruses to mammals has been evolving since the mid-1980s. Here, we demonstrate that H5N1 influenza viruses, isolated from apparently healthy domestic ducks ...in mainland China from 1999 through 2002, were becoming progressively more pathogenic for mammals, and we present a hypothesis explaining the mechanism of this evolutionary direction. Twenty-one viruses isolated from apparently healthy ducks in southern China from 1999 through 2002 were confirmed to be H5N1 subtype influenza A viruses. These isolates are antigenically similar to A/Goose/Guangdong/1/96 (H5N1) virus, which was the source of the 1997 Hong Kong "bird flu" hemagglutinin gene, and all are highly pathogenic in chickens. The viruses form four pathotypes on the basis of their replication and lethality in mice. There is a clear temporal pattern in the progressively increasing pathogenicity of these isolates in the mammalian model. Five of six H5N1 isolates tested replicated in inoculated ducks and were shed from trachea or cloaca, but none caused disease signs or death. Phylogenetic analysis of the full genome indicated that most of the viruses are reassortants containing the A/Goose/Guangdong/1/96-like hemagglutinin gene and the other genes from unknown Eurasian avian influenza viruses. This study is a characterization of the H5N1 avian influenza viruses recently circulating in ducks in mainland China. Our findings suggest that immediate action is needed to prevent the transmission of highly pathogenic avian influenza viruses from the apparently healthy ducks into chickens or mammalian hosts.
Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as ...angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.
Standalone renewable energy system holds the most promising solution to the electrification of remote areas without utility grid access as well as to reduce fossil fuel consumption and environmental ...pollution. However, the random volatility and unpredictability of renewable energy are key factors to restrict its large-scale accommodation. In the present study, a multi-objective mean-semi-entropy model is proposed for a standalone micro-grid with photovoltaic-wind-battery-diesel generator hybrid system, with the aim of providing a trade-off solution between maximum profits and minimum risk in consideration of photovoltaic and wind uncertainties. Then, the preference-inspired co-evolutionary algorithm, along with Pareto optimality concept, is used for the system techno-economic optimization, i.e., to maximize the profits defined as the mean value of the return and to minimize the risk defined as the semi-entropy simultaneously. Subsequently, the preference ranking organization method is used for decision making to determine the optimal trade-off dispatch solution. Simulation results show that the multi-objective mean-semi-entropy model is well applicable to deal with standalone micro-grid operation, considering the integration of uncertain renewable energy resources.
•A planning method for standalone micro-grid with uncertain wind and photovoltaic power is investigated.•A multi-objective mean-semi-entropy model for optimal standalone micro-grid operation is proposed.•An optimal dispatch solution from the perspective of risk aversion and profit maximization is studied.•Different models are employed for comparison to fully evaluate the effectiveness of the proposed model.
The effects of dietary lipids and Clostridium butyricum on carcass quality, fat deposition, meat quality, and fatty acid contents of breast meat in broiler chickens were investigated. One hundred ...sixty one-day-old broiler chicks (Arbor Acres) were divided into 4 treatment groups in a 2 x 2 factorial arrangement and fed 4 diets with 2 lipid sources (soybean oil or fish oil) and 2 levels of C. butyricum (0 or 5 g/kg of diets) were used. Abdominal fat was significantly reduced when chicks were fed the fish oil diet compared with the soybean oil diet (P < 0.01). Fish oil diets increased drip losses of the breast and thigh muscles, thawing losses of breast muscle, and boiling losses of thigh muscle (P < 0.05). Moreover, the C. butyricum diet profoundly reduced shear force of muscle (P < 0.05). The supplementation of C. butyricum increased i.m. fat, the contents of C20:5n-3 (P < 0.05), and total n-3 polyunsaturated fatty acids (P < 0.05) in breast muscle. Additionally, there were significant interactions between lipids and C. butyricum for drip losses of breast muscle (P < 0.01) and boiling losses of thigh muscle (P < 0.05) and for the contents of C20:5n-3 (P < 0.05) and n-3 polyunsaturated fatty acids (P < 0.05) of breast muscle. The results of this study indicate that dietary inclusion of C. butyricum improves meat quality and fatty acid profiles of breast meat in male broilers, particularly interacting with a fish oil diet.
Laboratory of genetics and physiology 2 (LGP2) is an important intracellular receptor that recognizes viral RNAs in innate immunity. In this study, a novel LGP2 cDNA was identified from the spleen of ...a Muscovy duck (Cairina moschata). The deduced amino acid sequence of Muscovy duck LGP2 (
MdLGP2
) consisted of 675 amino acid residues. The peptide contained two main structure domains: six important motifs, including a DExD/H box for RNA helicase activity in the RNA helicase region located at the N-terminal region, and two Zn2+-binding regions with an RNA-binding loop in the C-terminus regulatory domain (CTD). The MdLGP2 mRNA was ubiquitously expressed in the tested tissues, with high expression levels in glandular stomach, colon, ileum, crop, and caecum tissues, and low expression levels in the brain, skin, and heart. The mRNA expression of MdLGP2 was significantly upregulated in the brain, spleen, and lungs of ducks in the early stages of postinfection with H5N1 highly pathogenic avian influenza virus (HPAIV). These results suggested that MdLGP2 was involved in the early stages of antiviral innate immune response in ducks after infection with H5N1 HPAIV. However, whether it plays a positive or negative regulatory role in the host antiviral response requires further investigation.
Two experiments were conducted to assess the effects of media pH and mixtures (SCEF) of live yeast Saccharomyces cerevisiae (SC) and lactic acid bacteria Enterococcus faecium (EF) on gas production ...(GP), dry matter disappearance (DMD), and volatile fatty acid (VFA) concentrations in batch culture using either high-forage (HF) or high-grain (HG) diets. Diets were evaluated in separate experiments, each as a complete randomized design with 2 (media pH 5.8 and 6.5) × 5 (control, three SCEF, monensin) factorial arrangement of treatments. The SCEF had varying ratios of SC:EF: 0:0 (control), 1.18:1 (SCEF1), 1.25:1 (SCEF2), and 1.32:1 (SCEF3), added on a log10 basis. For the HF diet, supplementation of SCEF had greater GP (P = 0.03) at pH 6.5 and greater DMD (P = 0.03) and VFA concentration (P < 0.01) at pH 5.8 and 6.5 than control. For the HG diet, acetate:propionate (A:P) ratio at pH 6.5 was greater (P = 0.05) for SCEF than control. Increasing ratio of SC to EF in SCEF linearly (P < 0.01) decreased GP and DMD and linearly increased acetate percentage at pH 6.5. These results suggest that optimizing the SC:EF ratio in a mixture of SCEF can help improve rumen fermentation.
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