Effects of supplementation of rumen-protected choline on growth performance,meat quality and gene expression in longissimus dorsi muscle of lambs

This study determined the effects of rumen-protected choline (RPC) on growth performance, blood lipids, meat quality and expression of genes involved in fatty-acid metabolism in young lambs. A total of 24 Dorper × Hu lambs (about 20 kg body weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and 0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of lambs, whereas treatments had no significant effect on feed intake. The pH values of meat were increased at 0.25% RPC and both, dripping loss and shear force of meat, were significantly decreased in RPC-supplemented lambs. No significant changes were observed for dressing percentage and intramuscular fat. RPC supplementations had no significant effect on the concentrations of triglycerides and cholesterols in serum, but the concentration of high-density lipoprotein was decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75% RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and had no effect on CD36 gene. The results of this study showed that supplementation of 0.25% RPC could promote growth performance of lambs and improve meat quality. This may be mediated by effects on blood lipid profiles and the metabolism of fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC supplementation need to be validated with a larger number of animals. Higher doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC expression.     

HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway

The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.     

Plasma levels of kisspeptins in postmenopausal Chinese women do not show substantial elevation

The menopause, defined as the permanent cessation of menstruation resulting from ovarian failure, is characterized by elevated levels of serum gonadotropins. Recent studies have demonstrated that the gonadotropin hypersecretion in postmenopausal women is secondary to increase of KiSS-1 mRNA from the hypothalamus neurons, which encoded kisspeptin peptides. The present study was designed to determine whether plasma kisspeptins levels are altered in postmenopausal women. Blood samples were taken from 145 postmenopausal women, 35 young women and 30 pregnant women control in the first trimester. The plasma concentration of kisspeptins, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E₂) was measured using immunoassay kits. Results indicated that plasma kisspeptins levels in postmenopausal women had higher than those in young women (5.25 ± 0.36; 4.48 ± 0.34 pmol/L), but no significant difference was found between the two groups (p = 0.179). Plasma FSH and LH levels were significantly higher in postmenopausal women (124.67 ± 12.78, 57.14 ± 3.57 mIu/mL) than those in young women (9.23 ± 2.78, 7.56 ± 2.71 mIu/mL, p < 0.001). However, Plasma kisspeptins levels were not significantly correlated to FSH and LH in postmenopausal women (r = ?0.23, 0.324; p = 0.927, 0.176, respectively), and also there was no any correlation between plasma kisspeptins and E₂ in postmenopausal women (r = ?0.065; p = 0.792). Collectively, there was no significant difference in plasma kisspeptins levels between postmenopausal and young women. Our result suggested that kisspeptins’ role during menopause might mainly act in central rather than peripheral system and it could not be currently used as a clinical marker for menopause.     

Discovery of novel osthole derivatives as potential anti-breast cancer treatment

Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, was used as a lead compound for structural modification. A series of osthole derivatives bearing aryl substituents at 3-position of coumarin, has been prepared and evaluated for their growth inhibitory activity against human breast cancer cell lines MCF-7 and MDA-MB-231. Interestingly, some derivatives exhibited good inhibition, among them compound 8e was found to be the most potent compound with IC(50) values of 0.24 μM, 0.31 μM against MCF-7 and MDA-MB-231, respectively, which was improved more than 100-folds compared with its parent compound osthole.     

Discovery of novel 1-phenyl-cycloalkane carbamides as potent and selective influenza fusion inhibitors

A novel class of HA inhibitors (4a) was identified based on ligand similarity search of known HA inhibitors. Parallel synthesis and further structural modifications resulted in 1-phenyl-cyclopentanecarboxylic acid (4-cyano-phenyl)-methyl-amide 4t as a potent and selective inhibitor to phylogenetic H1 influenza viruses with an EC₅₀ of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.     

Hormonal regulation of uterine natural killer cells in mouse preimplantation uterus

Uterine Natural Killer (uNK) cells are the most abundant lymphocyte population recruited in the uteri during murine and human pregnancy. Previous investigation on uNK cells during mouse pregnancy focused more on its accumulation in postimplantation periods, which were believed to play important roles in regulating trophoblast invasion and angiogenesis towards successful placentation. However, by using recently developed methods of Dolichos biflorus agglutinin (DBA) lectin, a closer examination during mouse preimplantation revealed that there were also dynamic regulations of uNK cell, suggesting a major regulation by steroid hormones. Here we provide a detailed examination of uNK cells distribution during mouse early pregnancy by DBA lectin reactivity, with emphasis on preimplantation period and its hormonal regulation profiles. Our results showed that uNK precursor cells or its cell membrane specific components could be recruited in the uterus by estrogen or/and progesterone, and the effects could be completely abolished by specific antagonists of their nuclear receptors (estrogen and progesterone receptor). These results suggested that the preimplantation uterus, through concerted hormone regulation, could recruit uNK precursor cell or its specific cellular component, which might be conducive for uterine receptivity and further uNK construction/function during postimplantation.