Neonates are at increased risk for inflammatory bowel disease, but effective prevention and treatments are currently limited. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of dietary supplementation with alpha-ketoglutarate (AKG) on the intestinal morphology and function. Eighteen 24-day-old pigs (weaned at 21 days of age) were assigned randomly to control, LPS, and LPS + AKG groups. The piglets in the control and LPS groups were fed a corn- and soybean meal-based diet, whereas the LPS + AKG group was fed the basal diet supplemented with 1% AKG. On days 10, 12, 14, and 16, piglets in the LPS and LPS + AKG groups received intraperitoneal administration of LPS (80 microg/kg BW), whereas piglets in the control group received the same volume of saline. On day 16, D-xylose was orally administrated to all pigs at the dose of 0.1 g/kg BW, 2 h after LPS or saline injection, and blood samples were collected 3 h thereafter. Twenty-four hours post-administration of LPS or saline, pigs were killed to obtain intestinal mucosae for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) protein levels, the ratio of villus height to crypt depth, and the ratio of phosphorylated mTOR to total mTOR in duodenal, jejunal, and ileal mucosa. These adverse effects of LPS were attenuated (P < 0.05) by AKG supplementation. Moreover, AKG prevented the LPS-induced increase in intestinal HSP70 expression. Collectively, these novel results indicate that dietary supplementation with 1% AKG activates the mTOR signaling, alleviates the mucosal damage, and improves the absorptive function of the small intestine in LPS-challenged piglets. The findings not only help understand the mode of AKGs actions in the neonatal gut but also have important implications for infant nutrition under inflammatory conditions.
The present study determined whether a-ketoglutarate (AKG) might affect the expression of AMP-activated protein kinase (AMPK) and energy status in the intestinal mucosa of piglets challenged with Escherichia coli lipopolysaccharide (LPS). A total of eighteen piglets (weaned at 21 d of age) were allocated to one of three treatments: (1) non-challenged (control); (2) LPS-challenged (LPS); (3) LPS þ 1 % AKG (LPS þ AKG). Piglets in the control and LPS groups were fed a maize-and soyabean meal-based diet, and the LPS þ AKG group was fed the basal diet supplemented with 1 % AKG. On days 10, 12, 14 and 16 of the trial, piglets in the LPS and LPS þ AKG groups were challenged with LPS (80 mg/kg body weight), whereas piglets in the control group received the same volume of sterile saline. Pigs were euthanised 24 h after the last administration of LPS or saline to obtain intestinal mucosae for biochemical analysis. Compared with the control group, LPS administration decreased (P,0·05) the oxidation of AKG, oleic acid, glutamine and glucose in enterocytes, decreased concentrations of ATP in the duodenal and jejunal mucosae and decreased adenylate energy charge (AMP:ATP ratio) in the jejunal and ileal mucosae. Additionally, LPS treatment reduced (P,0·05) mucosal concentrations of phosphorylated AMPK in the jejunum and ileum as well as acetyl-CoA carboxylase in all segments of the small intestine. The adverse effects of LPS were reversed by AKG. Collectively, these results indicate that dietary supplementation with 1 % AKG beneficially modulates the AMPK signalling pathway to improve energy status in the small intestine of LPS-challenged piglets.Key words: : a-Ketoglutarate: Intestinal mucosae: AMP-activated protein kinase signalling: Piglets: Lipopolysaccharide a-Ketoglutarate (AKG) is an intermediate in the citric acid cycle as well as a precursor of glutamate and glutamine (1) , therefore potentially playing an important role in intestinal energy metabolism (2,3) . Emerging evidence shows that, similar to glutamine (4) , AKG can regulate gene expression and the mammalian target of rapamycin signalling pathway in the pig intestine (5) . There is also a suggestion that AKG may have a sparing effect on glutamate and aspartate in cells by serving as a fuel source (6,7) , and these amino acids are important for arginine metabolism in young pigs (8) . Consistent with these previous reports, we have recently demonstrated that dietary supplementation with 1 % AKG improved small-intestinal histological morphology and absorptive function in weanling piglets challenged with lipopolysaccharide (LPS) (5) . However, little is known about the molecular mechanisms responsible for the action of AKG on the small intestine. In the present study, we focused on small-intestinal energy status, because the gut has a high requirement for ATP to support intestinal integrity, function (including nutrient digestion and absorption) and health (1,3) .AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase consisting of three s...
The high-temperature mechanical properties of twinning-induced plasticity (TWIP) steel with 0.05 % C, 25 % Mn, 3 % Al, 3 % Si have been investigated using the GLEEBLE 3500 machine. The result shows that the zero ductility temperature and the zero strength temperature of the TWIP steel are measured at 1,225 °C and 1,275 °C, respectively. The brittleness temperature interval I is from 1,200 °C to the melting point, and the brittleness temperature interval III is from 650 °C to 800 °C. The tensile fracture has been examined using the scanning electron microscope, optical microscope and electron backscatter diffraction to determine the fracture mechanisms. The result shows that the twin is not the main influencing factor of the high-temperature plasticity of TWIP steel. Instead, the degree of dynamic recrystallization determines its high-temperature plasticity. A small number of AlN particles are found near the fractures, but these particles are so coarse, therefore, have no influence on the brittle fracture, and ferrite transformation and work hardening are the main reasons that cause the brittle fracture.
The fabrication of structural mimetic scaffolds reinforced with multi-angle silk fibers is described. Degummed silk fibers with a parallel arrangement of the fibers in a planar format were overlapped with successive layers organized at 0°, 30°, 60° and 90°, respectively. The overlapped silk fiber layers were coated with silk solution (6 wt%) containing sodium dodecyl sulfate (SDS). The morphology, mechanical properties, structure and biocompatibility of the scaffolds were investigated. The mechanical properties of the scaffolds (tensile and burst) were characterized based on the angles of the fibers. Layers with an overlapping angle at 30° exhibited better mechanical performance (18 MPa) than the other groups. The results of Fourier Transform (FT) IR Spectroscopy (FT-IR) and X-ray Differentiation (XRD) analyses indicated that the presence of degummed silk fibers with different angles did not significantly impact secondary structure or crystallization of the fiber reinforced scaffolds. The attachment and growth of a human fibroblast cell line (HS-865-SK) on the reinforced scaffolds supported good cell compatibility. These new scaffolds have potential applications in tissue repairs where superior mechanical strength and cell compatibility are important.
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