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    Determination of the trace minerals requirements for maintenance and growth of 35-50 kg Dorper x Hu crossbred ram lambs
    (Taylor & Francis Ltd, 2020) Zhang, Hao; Zhang, Ying; Peng, Along; Nie, Haitao; Wang, Feng; Elsabagh, Mabrouk; Loor, Juan J.
    This study aimed at estimating the trace minerals net requirements for maintenance and growth of Dorper x Hu ram lambs using the comparative slaughter techniques in 35 lambs of 35-50 kg body weight (BW). Seven lambs were slaughtered at the initial BW (34.93 +/- 0.37 kg) to determine the basal whole-body composition. Another seven lambs were fed ad libitum (AL) and then slaughtered when it reached 41.73 +/- 0.53 kg BW. The remained 21 lambs were assigned into three treatment groups, seven animals each, and fed 100, 70 or 40% of AL intake, respectively, and were slaughtered when they reached a BW of 49.93 +/- 1.03 kg. The net requirements of maintenance were 5.1, 429.3, 94.0 and 48.8 mu g/kg empty BW (EBW) for Mn, Fe, Zn and Cu, respectively. The net requirements of growth at 35 kg BW were 0.86, 70.41, 33.46 and 4.31 mg/kg EBW for Mn, Fe, Zn and Cu, respectively. At a BW of 50 kg, the net growth requirements were 0.93, 68.40, 35.20 and 4.15 mg/kg EBW for Mn, Fe, Zn and Cu, respectively. Our data indicated that the Mn and Zn requirements increase, whereas those of Fe and Cu decrease when BW increases. In addition, the net Cu, Mn and Fe requirements for maintenance and Zn, Cu, Mn and Fe requirements for growth of Dorper x Hu hybrid ram lambs were higher than those reported in the NRC but Zn requirements for maintenance matched that of the NRC.
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    Dietary rumen-protected L-arginine or N-carbamylglutamate attenuated fetal hepatic inflammation in undernourished ewes suffering from intrauterine growth restriction
    (Keai Publishing Ltd, 2021) Zhang, Hao; Zhang, Ying; Ma, Yi; Elsabagh, Mabrouk; Wang, Hongrong; Wang, Mengzhi
    This study aimed to explore whether dietary rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation (IUGR) in ovine fetuses. On d 35 of pregnancy, twin-bearing Hu ewes (n = 32) were randomly assigned to 4 treatment groups (8 ewes and 16 fetuses per group) and fed diets containing 100% of the NRC requirements (CON), 50% of the NRC requirements (RES), RES + RP-Arg (20 g/d) (RESA), or RES + NCG (5 g/d) (RESN). At 08:00 on d 110 of gestation, fetal blood and liver tissue samples were collected. The levels of triglyceride, free fatty acid, cholesterol and beta-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower (P < 0.05) than those of the RES group, but were higher (P < 0.05) than those of the CON group. The interleukin (IL)6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88 (MyD88), transforming growth factor beta (TGF beta), and nuclear factor kappa B (NF-kB) mRNA levels in the fetal liver were decreased (P < 0.05) by the NCG or RP-Arg supplementation compared to the RES treatment. Similarly, the toll-like receptor (TLR)-4, MyD88, TGFb, and p-c-Jun N-terminal kinase (JNK) protein levels in the fetal liver were reduced (P < 0.05) in the NCG and RP-Arg-supplemented groups compared to the RES group. These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism, down-regulating the TLR-4 and the inflammatory JNK and NF-kB signaling pathways, and decreasing cytokine production in ovine fetal blood and liver tissue. (C) 2021 Chinese Association of Animal Science and Veterinary Medicine. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.
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    Effects of the Gut Microbiota and Barrier Function on Melatonin Efficacy in Alleviating Liver Injury
    (Mdpi, 2022) Zhang, Hao; Liu, Xiaoyun; Elsabagh, Mabrouk; Zhang, Ying; Ma, Yi; Jin, Yaqian; Wang, Mengzhi
    Environmental cadmium (Cd) exposure has been associated with severe liver injury. In contrast, melatonin (Mel) is a candidate drug therapy for Cd-induced liver injury due to its diverse hepatoprotective activities. However, the precise molecular mechanism by which Mel alleviates the Cd-induced liver injury, as well as the Mel-gut microbiota interaction in liver health, remains unknown. In this study, mice were given oral gavage CdCl2 and Mel for 10 weeks before the collection of liver tissues and colonic contents. The role of the gut microbiota in Mel's efficacy in alleviating the Cd-induced liver injury was evaluated by the gut microbiota depletion technique in the presence of antibiotic treatment and gut microbiota transplantation (GMT). Our results revealed that the oral administration of Mel supplementation mitigated liver inflammation, endoplasmic reticulum (ER) stress and mitophagy, improved the oxidation of fatty acids, and counteracted intestinal microbial dysbiosis in mice suffering from liver injury. It was interesting to find that neither Mel nor Cd administration induced any changes in the liver of antibiotic-treated mice. By adopting the GMT approach where gut microbiota collected from mice in the control (CON), Cd, or Mel + Cd treatment groups was colonized in mice, it was found that gut microbiota was involved in Cd-induced liver injury. Therefore, the gut microbiota is involved in the Mel-mediated mitigation of ER stress, liver inflammation and mitophagy, and the improved oxidation of fatty acids in mice suffering from Cd-induced liver injury.
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    Effects of the maternal gut microbiome and gut-placental axis on melatonin efficacy in alleviating cadmium-induced fetal growth restriction
    (Academic Press Inc Elsevier Science, 2022) Zhang, Hao; Liu, Xiaoyun; Zheng, Yi; Zha, Xia; Elsabagh, Mabrouk; Zhang, Ying; Ma, Yi
    Cadmium (Cd) is a major environmental stressor that induces fetal growth restriction (FGR). Also, changes in gut microbiome diversity-which can be modulated positively by melatonin (Mel) have implications on fetal development and placental functions. Therefore, this study aimed to explore whether the role of Mel in counteracting the Cd-induced FGR by regulating placental barrier injury, endoplasmic reticulum stress (ERS) and mitophagy in pregnant mice is mediated-in part-via the gut microbiota modulations. Pregnant mice were intraperitoneally injected with CdCl2 (5 mg/kg) and Mel (5 mg/kg) once daily, respectively, at the same time from gestational day (GD) 8 to GD18, and then the maternal colon and placental tissues were collected for detection. To investigate the inner relationship between intestinal flora and the protection of Mel on FGR caused by Cd, gut microbiota transplantation (GMT) was carried out from GD0 to GD18 after the removal of intestinal microbiota by antibiotics. Results indicated that Mel relieved barrier injury, ERS and mitophagy in the placenta, and reversed the maternal gut microbiota dysbiosis. The GMT approach suggested a role of intestinal microbiota in placental barrier injury, ERS and mitophagy induced by Cd. Overall, the results highlighted that the intestinal microbiota and gut-placental axis play a central role in the protective effect of Mel against Cd-induced FGR.
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    L-Arginine inhibits hydrogen peroxide-induced oxidative damage and inflammatory response by regulating antioxidant capacity in ovine intestinal epithelial cells
    (Taylor & Francis Ltd, 2021) Zhang, Hao; Zhang, Ying; Liu, Xiaoyun; Elsabagh, Mabrouk; Yu, Yin; Peng, Along; Dai, Sifa
    Little is known how L-arginine (Arg) affects the ovine intestinal epithelial cells (IOECs) redox status induced by hydrogen peroxide (H2O2)(.) This study aimed to examine the impact of Arg on IOECs subjected to H2O2-induced oxidative damage, intestinal barrier injury, and inflammatory response. The IOECs were incubated for 16 h then classified as four groups (n = 6/group) and cultured in corresponding media including (1) control (CON) group, in which IOECs were cultured in Arg-free Dulbecco's modified Eagle's F12 Ham medium (DMEM) containing 100 mu M Arg; (2) Arg group, in which IOECs were cultured in Arg-free DMEM containing 350 mu M Arg; (3) H2O2 group, in which IOECs were cultured in CON group plus 150 mu M H2O2; (4) Arg + H2O2 group, in which IOECs were cultured in Arg group plus150 mu M H2O2. After culturing for 24 h in media, some characteristics of cells in the four groups were measured. Arg administration decreased the H2O2-induced reactive oxygen species (ROS) production compared with the H2O2 group (p < .05). Compared with H2O2, adding Arg to H2O2 increased (p < .05) transepithelial electrical resistance (TEER), but decreased (p < .05) tumour necrosis factor alpha (TNF-alpha) within the IOECs. Compared with H2O2, adding Arg to H(2)O(2-)induced injured IOECs increased (p < .05) glutathione peroxidase 1 (GPx1), zonula occludens-1 (ZO-1), and epithelial nitric oxide (NO) synthase (eNOS) protein levels, and decreased (p < .05) TNF-alpha levels within cells. Arg inhibits H2O2-induced oxidative damage, intestinal barrier injury, and inflammatory response by NO pathway within IOECs.