かつおだし摂取のマウスの情動行動及び脳内パルブアルブミン陽性ニューロンに及ぼす影響

富山大学・富生命博甲第88号・Jargalsaikhan Undarmaa・2017/03/23Nutritional Neuroscience,Published online:21 Jul 2016,1-16,doi:10.1080/1028415X.2016.1208429に掲載富山大学201

Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

BACKGROUND: One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. METHODS: The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. RESULTS: uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. CONCLUSION: These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients

Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios

Genetic variation and diversity of pearl millet [Pennisetum glaucum (L.)] genotypes assessed for millet head miner, Heliocheilus albipunctella resistance, in West Africa

Pearl millet (Pennisetum glaucum L.), the major source of minerals and dietary energy for people living in the semi-arid regions of Sahel, is regularly damaged by millet head miner, Heliocheilus albipunctella. In order to identify the plant-based resistance sources for millet head miner along with high grain Fe and Zn, we have screened forty pearl millet genotypes, using an artificial infestation method. Analysis of variance revealed significant differences in the genotypes tested for head miner resistance. The genotypes Gamoji, ICMP 177001, ICMP 177002, ICMV 177003, ICMV IS 90311, LCIC9702, Souna 3, ICMV IS 94206 and PE08043 exhibited antibiosis resistance mechanism to Heliocheilus albipunctella with appreciable agronomy and grain yield when compared with the susceptible check ICMV IS 92222. The genotypes Faringuero, ICMV 167005, ICMV IS 99001, Sadore local, SOSAT-C88, and ICMP 177004 exhibited tolerance to head miner damage with good per se performance. The genotypes ICMP 177001, ICMP 177002, ICMV 177003, and Moro exhibited resistance to millet head miner and had consistent grain Fe content across seasons (ranging from 44 to 70 ppm). Association between the head miner resistance and morphological traits showed a positive and significant correlation of larval production index (%) with head miner damage (r = 0.59**). Grain Fe and Zn contents exhibited negative association with panicle length and grain yield indicating proper care should be taken in breeding for these traits. Hence, the identified resistance sources can be effectively utilized in breeding head miner resistant pearl millet OPV’s/ hybrids, with high grain yield including Fe and Zn concentrations, to overcome the hunger and malnutrition seen in populations living in the semi-arid tropics

Rapid fucosylation of intestinal epithelium sustains host–commensal symbiosis in sickness

Systemic infection induces conserved physiological responses that include both resistance and ‘tolerance of infection’ mechanisms. Temporary anorexia associated with an infection is often beneficial, reallocating energy from food foraging towards resistance to infection or depriving pathogens of nutrients. However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin (IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host’s resources to maintain host–microbial interactions during pathogen-induced stress