Beneficial Effects of the Consumption of Hot-Water Extracts of Thinned Immature Mangos (Mangifera indica "Irwin") on the Hypertriglyceridemia of Apolipoprotein E-Deficient Mice.

The thinned immature fruit of the mango tree (Mangifera indica "Irwin") are regarded as waste products. In this study, we evaluated the effects of daily consumption of a hot-water extract of thinned immature mango fruits (TIMEx) on the dyslipidemia of apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice and wild-type BALB/c mice were fed a 20% fat diet containing 0%, 0.1%, or 1.0% TIMEx for 8 weeks. Their body mass, food intake, and water consumption were unaffected by the TIMEx. The 1.0% TIMEx supplementation significantly reduced serum triglyceride, but not total cholesterol concentration. This effect was significant in ApoE-/- mice, but less marked under normal conditions in wild-type mice. In addition, the circulating concentrations of three hormones that regulate metabolism, resistin, leptin, and glucose-dependent insulinotropic polypeptide, were reduced by TIMEx consumption, which may be involved in its effect to prevent hypertriglyceridemia. However, none of the concentrations of TIMEx reduced the size of atherosclerotic plaque lesions. In conclusion, daily consumption of TIMEx ameliorates hypertriglyceridemia but not hypercholesterolemia in genetically predisposed mice.

Selective Consumption of Fish Oil at End of the Day Increases the Physiological Fatty Acid Compositions of Eicosapentaenoic Acid and Docosahexaenoic Acid in Mice.

Diets with high daily fat consumption are associated with excess weight. However, the effects of fat type and consumption timing on excess weight remain unclear. We investigated the selection of a 30% (w/w) fat diet of soybean oil (SOY), lard (LARD), and fish oil (FISH) on the metabolic parameters of mice. Male C57BL/6 mice were divided into the double SOY-box (w-SOY), SOY-box/LARD-box (SOY-vs-LARD), or SOY-box/FISH-box (SOY-vs-FISH) groups and allowed to selectively consume for 8 weeks. The total energy intake was similar for all groups, but the mice selectively chose to consume LARD over SOY and SOY over FISH. Body weight in the SOY-vs-LARD group was significantly higher than that in the w-SOY and SOY-vs-FISH groups. Additionally, minimal but selective consumption of an omega-3 fatty-acid-rich FISH diet at the end of the active period increased the physiological fatty acid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the SOY-vs-FISH group; their metabolic parameters were also lower than the SOY-vs-LARD group. In conclusion, selectively consuming small amounts of fish oil at the end of the day may prevent excess weight compared with LARD consumption.

Insulin-like growth factor-1 induces IRE1-XBP1-dependent endoplasmic reticulum biogenesis in bovine mammary epithelial cells.

Insulin-like growth factor-1 (IGF-1) plays a key role in proliferation and galactopoiesis in mammary epithelial cells (MEC), but its definitive functions on endoplasmic reticulum (ER) during protein synthesis remain unknown. The present study aimed to elucidate the effects of IGF-1 on ER biogenesis in MEC in vitro and examined the expression of ER biogenesis-associated genes in the mammary gland during early lactation. We treated mammary alveolar cells-large T antigen cells (immortalized bovine MEC line established via stable transfection with simian virus-40 large T-antigen) with IGF-1 and examined ER biogenesis using the fluorescence intensity of an ER tracker and quantitative real-time PCR. We found IGF-1 significantly increased ER tracker staining and upregulated mRNA levels of ER biogenesis-related genes, such as CHKA (choline kinase α), PCYT1A (choline-phosphate cytidylyltransferase A), and SURF4 (surfeit locus protein 4). We focused on unfolded protein response to explore molecular mechanisms by which IGF-1 induces ER biogenesis. We found IGF-1 significantly increased mRNA levels of the XBP1 splicing form (XBP1s). Based on western blot analysis, IGF-1 induced the expression of (inositol-requiring kinase 1 α) protein, upstream of XBP1s, and phosphorylated-IRE1α. The inhibition of IRE1 endoribonuclease activity with 4-methylumbelliferone 8-carbaldehyde (4µ8C) significantly suppressed the increase in ER tracker fluorescence and ER biogenesis-related gene expression induced by IGF-1. Also, IGF-1-induced XBP1s and ER biogenesis-associated gene expression was inhibited by rapamycin, an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), indicating that IRE1-XBP1 activation by IGF-1 is mediated by mTORC1. Moreover, to clarify the expression of XBP1s and ER biogenesis-associated genes expression under normal physiological conditions, mammary gland tissue from biopsies of dairy cows during late gestation and lactation were analyzed. In vivo data highlighted the significant increases in the mRNA levels of XBP1s and ER biogenesis-related genes in mammary gland tissue immediately after calving through 6 wk of lactation. The mRNA levels of IGF1R (IGF-1 receptor) in mammary glands increased during 6 wk of lactation. Therefore, the present study indicated for the first time that IGF-1 induces ER biogenesis by activating the IRE1-XBP1 axis under the regulation of mTORC1 in bovine MEC line.

Anthocyanin and proanthocyanidin contents, antioxidant activity, and in situ degradability of black and red rice grains.

OBJECTIVE: An experiment was conducted to assess the antioxidant contents and activities of colored rice grains and to evaluate their nutritive characteristics in terms of chemical composition and in situ ruminal degradation. METHODS: Ten cultivars of colored rice grains (Oryza sativa L.) collected from several areas of Japan were studied, and control rice without pigment, maize, barley, and wheat grains were used as control grains. Their chemical compositions, pigment, polyphenol contents, total antioxidant capacity (TAC), and degradation characteristics were determined. RESULTS: The starch contents of the colored rice grains were in the range of 73.5% to 79.6%, similar to that of the control rice grain. The black and red rice grains contained anthocyanin (maximum: 5,045.6 µg/g) and proanthocyanidin (maximum: 3,060.6 µg/g) at high concentrations as their principal pigments, respectively. There were significantly (p<0.05) positive relationships among the pigment contents, polyphenol content, and TAC values in the colored and control rice grains, indicating that the increase in pigment contents also contributed to the increased polyphenol content and TAC values in the colored rice grains. The dry matter and starch degradation characteristics, as represented by c (fractional degradation rate of slowly degradable fraction) and by the effective degradability, of the colored rice grains and the control rice grain were ranked as follows among commonly used grains: wheat>barley ≥rice>maize. The colored rice grains also included the most-digestible starch, since their potential degradable fraction and actual degradability at 48 h incubation were almost 100%. CONCLUSION: Colored rice grains have high potential to be used as antioxidant sources in addition to starch sources in ruminants.

Enantioselective Collision-Activated Dissociation of Gas-Phase Tryptophan Induced by Chiral Recognition of Protonated L-Alanine Peptides.

Enantioselective dissociation in the gas phase is important for enantiomeric enrichment and chiral transmission processes in molecular clouds regarding the origin of homochirality in biomolecules. Enantioselective collision-activated dissociation (CAD) of tryptophan (Trp) and the chiral recognition ability of L-alanine peptides (L-Ala n ; n = 2-4) were examined using a linear ion trap mass spectrometer. CAD spectra of gas-phase heterochiral H+(D-Trp)(L-Ala n ) and homochiral H+(L-Trp)(L-Ala n ) noncovalent complexes were obtained as a function of the peptide size n. The H2O-elimination product was observed in CAD spectra of both heterochiral and homochiral complexes for n = 2 and 4, and in homochiral H+(L-Trp)(L-Ala3), indicating that the proton is attached to the L-alanine peptide, and H2O loss occurs from H+(L-Ala n ) in the noncovalent complexes. H2O loss did not occur in heterochiral H+(D-Trp)(L-Ala3), where NH3 loss and (H2O + CO) loss were the primary dissociation pathways. In heterochiral H+(D-Trp)(L-Ala3), the protonation site is the amino group of D-Trp, and NH3 loss and (H2O + CO) loss occur from H+(D-Trp). L-Ala peptides recognize D-Trp through protonation of the amino group for peptide size n = 3. NH3 loss and (H2O + CO) loss from H+(D-Trp) proceeds via enantioselective CAD in gas-phase heterochiral H+(D-Trp)(L-Ala3) at room temperature, whereas L-Trp dissociation was not observed in homochiral H+(L-Trp)(L-Ala3). These results suggest that enantioselective dissociation induced by chiral recognition of L-Ala peptides through protonation could play an important role in enantiomeric enrichment and chiral transmission processes of amino acids.

Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury. METHODS: The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined. RESULTS: ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation. CONCLUSION: Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.

Fas ligand released by activated monocytes causes apoptosis of lung epithelial cells in human acute lung injury model in vitro.

Alveolar epithelial cell death plays a crucial role in the progression of acute lung injury. We have demonstrated up-regulation of Fas expression on alveolar epithelial cells, and soluble Fas ligand secretion from inflammatory cells upon acute lung injury. Here we show that the lipopolysaccharide-stimulated human monocyte cell line THP-1 releases Fas ligand, and that conditioned medium from lipopolysaccharide-stimulated THP-1 cells induces apoptosis of the human pulmonary adenocarcinoma cell line A549. Activation of caspase-3 and -8 is associated with the apoptosis. Gene targeting on Fas in A549 cells by specific small interfering RNA impairs apoptosis induced by conditioned medium from activated THP-1, while that on Fas ligand in THP-1 cells impairs the apoptosis-inducing activity of the conditioned medium produced by lipopolysaccharide-stimulated cells. These results suggest that Fas ligand released by monocytes causes alveolar epithelial cell death through a Fas-dependent apoptotic mechanism in the development of acute lung injury.

Collateral uterine blood flow in Holstein cows during the third trimester of pregnancy.

Blood flow to the gravid and nongravid uterine horns of four multiparous Holstein cows (mean +/- SD, BW=641.8 +/- 95.4 kg; age=4.8 +/- 1.2 years; parity=3.0 +/- 1.2) was measured on days 225, 248, and 266 of gestation. Surgery was conducted on day 214.5 +/- 4.0 of gestation through the flank of the standing cows. Transit-time ultrasonic flow probes (diameter 12 or 14 mm) were fitted surgically around the uterine arteries of each cow. Surgery was completed within two hours of anesthesia, and the animals recovered rapidly following surgery. Uterine blood flow (UBF, l/min) was recorded at 10 sec intervals for approximately 23.5 hours; these values were averaged to determine UBF. The mean gravid UBF was significantly (P<0.05) greater than the nongravid UBF in this study. The range of the gravid and nongravid UBFs varied from 3.61 to 14.05 and 0.72 to 6.54 l/min, respectively. There were no changes (P>0.1) in the mean gravid and nongravid UBFs from day 225 to 266 of gestation.

Upright posture reduces thermogenesis and augments core hypothermia.

UNLABELLED: We recently reported that baroreceptor-mediated reflexes modulate thermoregulatory vasoconstriction during lower abdominal surgery. Accordingly, we examined the hypothesis that postural differences and the related alterations in baroreceptor loading similarly modulate the thermogenic (i.e., shivering) response to hypothermia in humans. In healthy humans (n = 7), cold saline was infused IV (30 mL/kg at 4 degrees C) for 30 min to decrease core temperature. Each participant was studied on 2 separate days, once lying supine and once sitting upright. Tympanic membrane temperature and oxygen consumption were monitored for 40 min after each saline infusion. The decrease in core temperature upon completion of the infusion in the upright posture position was 1.24 degrees C +/- 0.07 degrees C, which was significantly greater than the 1.02 degrees C +/- 0.06 degrees C seen in the supine position. The core temperature was reduced by 0.59 degrees C +/- 0.07 degrees C in the upright position but only by 0.37 degrees C +/- 0.05 degrees C in the supine position when the increase in oxygen consumption signaling thermogenic shivering occurred. Thus, the threshold temperature for thermogenesis was significantly less in the upright than the supine position. The gain of the thermogenic response did not differ significantly between the positions (363 +/- 69 mL. min(-1). degrees C(-1) for upright and 480 +/- 80 mL. min(-1). degrees C(-1) for supine). The skin temperature gradient was significantly larger in the upright than in the supine posture, suggesting that the peripheral vasoconstriction was augmented by upright posture. Plasma norepinephrine concentrations increased in response to cold saline infusion under both conditions, but the increase was significantly larger in the upright than in the supine posture. Baroreceptor unloading thus augments the peripheral vasoconstrictor and catecholamine response to core hypothermia but simultaneously reduces thermogenesis, which consequently aggravated the core temperature decrease in the upright posture. IMPLICATIONS: Upright posture attenuates the thermogenic response to core hypothermia but augments peripheral vasoconstriction. This divergent result suggests that input from the baroreceptor modifies the individual thermoregulatory efferent pathway at a site distal to the common thermoregulatory center or neural pathway.