MiR-1231 correlates tumor prognosis and inhibits cell growth in ovarian cancer.

OBJECTIVE: The purpose of this study was to investigate the expression characteristics of miR-1231 in ovarian cancer (OC), and to further explore its effects on cell proliferation capacity of OC cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was performed to detect miR-1231 expression in 116 paired of OC and matched adjacent normal tissues. The association of miR-1231 expression and clinicopathological features and prognosis was analyzed. Furthermore, the effects of miR-1231 on cell proliferation and cell cycle of OC cells were evaluated by functional assays. RESULTS: In the study, the results exhibited that miR-1231 expression was lower in ovarian cancer tissues compared with adjacent normal tissues. Lower miR-1231 expression was associated with tumor clinical stage and lymph node invasion in patients. Survival plots by K-M survival analysis showed that lower miR-1231 expression predicted a poor outcome in ovarian cancer patients. Moreover, multivariate analysis implied that miR-1231 expression was an independent maker of overall survival (OS). Functional assays showed that upregulation of miR-1231 expression inhibited cell proliferation and cell cycle progression. CONCLUSIONS: We revealed that miR-1231 expression was lower in ovarian cancer tissues cell lines. Lower miR-1231 expression predicted a poor outcome in ovarian cancer patients and upregulation of miR-1231 expression inhibited cell growth.

1H nuclear magnetic resonance-based plasma metabolomics provides another perspective of response mechanisms of newborn calves upon the first colostrum feeding.

The first meal of a neonatal calf after birth is crucial for survival and health. Blood IgG levels remarkably increase in neonatal calves after the first colostrum feeding. However, there is little comprehensive information on blood small-molecule metabolites in neonatal calves at that time. In this study, the changes in plasma metabolites of neonatal calves after the initial colostrum feeding were first examined with comprehensive 1H nuclear magnetic resonance (NMR). Sixteen plasma samples obtained from 8 calves before and after feeding were analyzed with 1H NMR. Multivariate analyses revealed a significant difference in metabolic profiles. After feeding, acute phase N-acetylated glycoproteins and 13 other plasma metabolites decreased, whereas 19 plasma metabolites increased. Metabolomics pathway analysis of these metabolites revealed that a global metabolic response on the first colostrum feeding was reflected by alterations of 13 metabolic pathways including lipid, carbohydrate, and amino acid metabolism in neonatal calves. These results suggested that besides meeting energy demand, a 4.0 L of high-quality colostrum feeding within 4 h after birth had a positive effect on relieving the postnatal stress in neonatal calves. This study provides another perspective of response mechanisms of newborn calves upon the first colostrum feeding.

Metabolomics and pathway analyses to characterize metabolic alterations in pregnant dairy cows on D 17 and D 45 after AI.

Nutrient flow to the embryo and placenta is crucial for proper development and growth during pregnancy. In this study, a metabonomic analysis was undertaken to better understand global changes in pregnant dairy cows on D 17 and D 45 after timed artificial insemination (AI). Metabolic changes in the blood plasma of pregnant dairy cows were investigated using HPLC-MS and a multivariate statistical analysis. Changes in metabolic networks were established using the MetPA method. Alterations in six metabolic pathways were found on D 17 and D 45, including variations in the level of alpha-linolenic acid metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, glycerolipid metabolism, folate biosynthesis, and tyrosine metabolism. In addition to these pathways, 9 metabolic pathways were markedly altered on D 45. These pathways included changes in the one-carbon pool caused by folate; phenylalanine, tyrosine and tryptophan biosynthesis; thiamine metabolism; pantothenate and CoA biosynthesis; purine metabolism; inositol phosphate metabolism; amino sugar and nucleotide sugar metabolism; pentose phosphate; and the TCA pathway. The combination of metabonomics and network methods used in this study generated rich biochemical insight into possible biological modules related to early pregnancy in dairy cows.

Dysprosium-bearing red cells as potential transverse relaxation agents for MRI.

The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted with saline and control cells to give an average dysprosium concentration of 3.3 +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased. R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2) increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2) was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture; R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the relaxivity effects were enhanced by sequestration of the dysprosium within intact red cells, and this effect was lost after lysis. At a circulating whole-blood concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped 29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium-loaded cells might be useful in the study of perfusion and tissue blood volume.

Intravascular susceptibility agent effects on tissue transverse relaxation rates in vivo.

Since vascular architecture differs among tissues, it was hypothesized that the change in transverse relaxation rate produced by a given tissue concentration of susceptibility contrast agent also varies by tissue. This is relevant to strategies to map regional blood volume by MRI using indicator dilution techniques. R*(2) was measured in rat organs over a range of susceptibility agent concentrations at 1.5 T. Rat red blood cells loaded with dysprosium-DTPA-BMA served as an intravascular susceptibility agent. Tissue samples were frozen in vivo and dysprosium concentrations were independently measured using inductively coupled plasma atomic emission spectroscopy. The slope (k) of R*(2) vs. tissue dysprosium concentration in sec(-1) mM(-1) for myocardium was 97.1 (95% C.I. 77. 0-117.2), liver 122.6 (108.3-136.9), spleen 22.5 (8.8-36.3), kidney 68.1 (58.6-77.6), and skeletal muscle 77.9 (4.1-151.6); k was significantly different (P < 0.05) for all pairings except those with skeletal muscle. Therefore, relative values of tissue blood volume derived from dynamic images of first pass contrast effects may be in error because k is not constant for different conditions.

Gadolinium-bearing red cells as blood pool MRI contrast agents.

Human and rat red blood cells (RBCs) were loaded with gadolinium DTPA dimeglumine using an osmotic pulse technique to create a blood pool contrast agent for MRI. The resulting packed red cells contained 30.9 +/- 3.3 (1 SD) mmol Gd/liter for humans and 24.7 +/- 3.5 (1 SD) mmol Gd/liter for rats. Longitudinal relaxation rate constant of human RBCs increased from 2.0 +/- 0.1 to 145.6 +/- 36.2 s(-1); the transverse relaxation rate constant increased from 6.8 +/- 1.2 to 562 +/- 410 s(-1). For rat RBCs, R1 increased from 1.45 +/- 0.15 to 84.8 +/- 23.9 s(-1); R2 increased from 7.1 +/- 0.64 to 247 +/- 158 s(-1). Affinity for oxygen was slightly reduced (control P50 = 22.3 +/- 2.3 versus experimental P50 = 27.3 +/- 1.3, P < 0.01), as was mechanical deformability. No drop in relaxivities was seen after 5 days of storage. The apparent volume of distribution was 0.0164 +/- 0.003 liter/kg, biologic half-life 4.38 +/- 0.34 h, and total plasma clearance 0.003 +/- 0.0006 liter/kg/h. Compared with Gd-DTPA "free" in the plasma, tissue enhancement from RBCs was initially lower but was much prolonged. Preparation is simple enough to be reproduced by most laboratories.